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1. Corrigendum: Topological Modification of Brain Networks Organization in Children With High Intelligence Quotient: A Resting-State fMRI Study

Author: Ilaria Suprano, Chantal Delon-Martin, Gabriel Kocevar, Claudio Stamile, Salem Hannoun, Sophie Achard, Amanpreet Badhwar, Pierre Fourneret, Olivier Revol, Fanny Nusbaum, Dominique Sappey-Marinier, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), RMN et optique : De la mesure au biomarqueur, Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nehme and Therese Tohme Multiple Sclerosis Center, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon, GIPSA - Vision and Brain Signal Processing (GIPSA-VIBS), Département Images et Signal (GIPSA-DIS), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Hospices Civils de Lyon (HCL), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre PSYRENE [Lyon], CERMEP - Imagerie du vivant, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Nehme and Therese Tohme Multiple Sclerosis Center [Beyrouth, Liban] (AUBMC), American University of Beirut Medical Center [Beyrouth, Liban] (AUBMC), American University of Beirut [Beyrouth] (AUB)-American University of Beirut [Beyrouth] (AUB), GIPSA - Communication Information and Complex Systems (GIPSA-CICS), Service de Psychopathologie du développement de l’enfant et de l’adolescent, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Lyon, France, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), This work was financially supported by the French National Research Agency, the Fondation APICIL, and the Shire International., Dojat, Michel, Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Computer science, Topology, 050105 experimental psychology, Lateralization of brain function, lcsh:RC321-571, [SCCO]Cognitive science, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, children, medicine, 0501 psychology and cognitive sciences, resting state, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Original Research, Artificial neural network, Resting state fMRI, Intelligence quotient, medicine.diagnostic_test, [SCCO.NEUR]Cognitive science/Neuroscience, Functional connectivity, [SCCO.NEUR] Cognitive science/Neuroscience, 05 social sciences, functional connectivity, hub disruption index, Correction, Graph theory, Human Neuroscience, [SCCO] Cognitive science, intelligence, brain networks, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Neurology, Graph (abstract data type), functional MRI, Functional magnetic resonance imaging, 030217 neurology & neurosurgery, Neuroscience
Abstract: This work was financially supported by the French National Research Agency, the Fondation APICIL, and the Shire International.; International audience; The idea that intelligence is embedded not only in a single brain network, but instead in a complex, well-optimized system of complementary networks, has led to the development of whole brain network analysis. Using graph theory to analyze resting-state functional MRI data, we investigated the brain graph networks (or brain networks) of high intelligence quotient (HIQ) children. To this end, we computed the "hub disruption index κ," an index sensitive to graph network modifications. We found significant topological differences in the integration and segregation properties of brain networks in HIQ compared to standard IQ children, not only for the whole brain graph, but also for each hemispheric graph, and for the homotopic connectivity. Moreover, two profiles of HIQ children, homogenous and heterogeneous, based on the differences between the two main IQ subscales [verbal comprehension index (VCI) and perceptual reasoning index (PRI)], were compared. Brain network changes were more pronounced in the heterogeneous than in the homogeneous HIQ subgroups. Finally, we found significant correlations between the graph networks' changes and the full-scale IQ (FSIQ), as well as the subscales VCI and PRI. Specifically, the higher the FSIQ the greater was the brain organization modification in the whole brain, the left hemisphere, and the homotopic connectivity. These results shed new light on the relation between functional connectivity topology and high intelligence, as well as on different intelligence profiles.
Published: 2020

2. In vivo targeting and multimodal imaging of cerebral amyloid-β aggregates using hybrid GdF3 nanoparticles

Author: Frédéric Lerouge, Elodie Ong, Hugo Rositi, Francis Mpambani, Lise-Prune Berner, Radu Bolbos, Cécile Olivier, Françoise Peyrin, Vinu K Apputukan, Cyrille Monnereau, Chantal Andraud, Frederic Chaput, Yves Berthezène, Bettina Braun, Mathias Jucker, Andreas KO Åslund, Sofie Nyström, Per Hammarström, K Peter R Nilsson, Mikael Lindgren, Marlène Wiart, Fabien Chauveau, Stephane Parola, Laboratoire de Chimie - UMR5182 (LC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Linköping University (LIU), Norwegian University of Science and Technology (NTNU), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-15-CE18-0026,NanoBrain,Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale(2015), and European Project: 242098,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,LUPAS(2009)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biomedical Engineering, Medicine (miscellaneous), multimodal imaging, General Materials Science, Bioengineering, luminescent-conjugated polythiophenes, Development, gadolinium fluoride nanoparticles, amyloid-beta
Abstract: Aim: To propose a new multimodal imaging agent targeting amyloid-β (Aβ) plaques in Alzheimer’s disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimer’s disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood–brain barrier status. Nevertheless, multimodal imaging showed successful Aβ targeting in both transgenic mice and Aβ fibril-injected rats.
Published: 2022

3. PCA-based approach for inhomogeneous PSF estimation and partial volume correction in PET

Author: Nicolas Costes, Bruno Mendez de Vigo, Hadj Batatia, Anthonin Reilhac, Zacharie Irace, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Université Toulouse - Jean Jaurès - UT2J (FRANCE), Université Toulouse 1 Capitole - UT1 (FRANCE), CERMEP - Imagerie du vivant (FRANCE), Fondation Neurodis (FRANCE), Institut de Recherche en Informatique de Toulouse - IRIT (Toulouse, France), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Fondation Neurodis, Traitement et Compréhension d’Images (IRIT-TCI), Institut de recherche en informatique de Toulouse (IRIT), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Institut National Polytechnique de Toulouse - INPT (FRANCE), (OATAO), Open Archive Toulouse Archive Ouverte, Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse Capitole (UT Capitole)
Subjects: Point spread function, Computer science, Partial volume, Deconvolution, 01 natural sciences, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Traitement des images, 0302 clinical medicine, 0103 physical sciences, Computer vision, Orthonormal basis, 010303 astronomy & astrophysics, Image restoration, Basis (linear algebra), business.industry, PET, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Principal component analysis, Partial volume effect, Artificial intelligence, business, Algorithm, Interpolation
Abstract: International audience; The quality of the measurements obtained in Positron Emission Tomography (PET) is severely limited by partial volume effects (PVE). This study proposes a Partial Volume Correction (PVC) technique that considers the spatial variability of the system's Point Spread Function (PSF) across the Field Of View (FOV). The proposed PSF model uses Principal Component Analysis to express their variability according to a small number of components called eigen-PSF, forming an orthonormal basis. The interpolation of the coordinates of these PSFs in this created basis allows their precise estimation across the FOV of the system. The resulting image degradation model can be expressed as a weighted sum of convolutions that can be integrated efficiently into classical PVC algorithms. Initial results shows accurate PSF estimation as well as significant image restoration.
Published: 2016

4. Non-invasive real-time access to spatial attention information from 3T fMRI BOLD signals

Author: Carine De Sousa Ferreira, Suliann Ben Hamed, Simon Clavagnier, Danielle Ibarrola, Franck Lamberton, Celia Loriette, Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cued speech, Computer science, business.industry, media_common.quotation_subject, [SCCO.NEUR]Cognitive science/Neuroscience, Cognition, Pattern recognition, Local field potential, computer.software_genre, Covert, Voxel, Contrast (vision), Artificial intelligence, Neurofeedback, business, computer, Decoding methods, media_common
Abstract: Access to higher cognitive functions in real-time remains very challenging, because these functions are internally driven and their assessment is based onto indirect measures. In addition, recent finding show that these functions are highly dynamic. Previous studies using intra-cortical recordings in monkeys, succeed to access the (x,y) position of covert spatial attention, in real-time, using classification methods applied to monkey prefrontal multi-unit activity and local field potentials. In contrast, the direct access to attention with non-invasive methods is limited to predicting the attention localisation based on a quadrant classification. Here, we demonstrate the feasibility to track covert spatial attention localization using non-invasive fMRI BOLD signals, with an unprecedented spatial resolution. We further show that the errors produced by the decoder are not randomly distributed but concentrate on the locations neighbouring the cued location and that behavioral errors correlate with weaker decoding performance. Last, we also show that the voxels contributing to the decoder precisely match the visual retinotopic organization of the occipital cortex and that single trial access to attention is limited by the intrinsic dynamics of spatial attention. Taken together, these results open the way to the development of remediation and enhancement neurofeedback protocols targeting the attentional function.
Published: 2022

5. Do femoral biomechanical properties follow locomotor changes in primates? An ontogenetic study of olive baboons ( Papio anubis )

Author: Quentin Cosnefroy, François Marchal, Laurence Bellaiche, Robert Carlier, Cyrille Cazeau, Franck Lamberton, Antoine Perrier, Jean‐Christophe Theil, Gilles Berillon, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Centre d'Imagerie Bachaumont-Montmartre, Clinique Victor Hugo, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Groupe Hospitalier Diaconesses Croix Saint-Simon, Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Histoire naturelle de l'Homme préhistorique (HNHP), and Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: International audience
Published: 2022

6. La biomécanique du fémur reflète-t-elle les comportements locomoteurs ? Étude de l’organisation structurelle de la diaphyse fémorale chez les catarrhiniens

Author: Cosnefroy, Quentin, Berillon, Gilles, Bellaiche, Laurence, Carlier, Robert, Cazeau, Cyrille, Chaumoître, Kathia, Lamberton, Franck, Perrier, Antoine, Theil, Jean-Christophe, Marchal, François, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Histoire naturelle de l'Homme préhistorique (HNHP), Muséum national d'Histoire naturelle (MNHN)-Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Centre d'Imagerie Bachaumont-Montmartre, Service d'Imagerie Médicale [Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Clinique Victor Hugo, Service de radiologie et imagerie médicale, hôpital Nord, CHU de Marseille, Assistance publique des Hôpitaux de Marseille, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Groupe Hospitalier Diaconesses Croix Saint-Simon, Université Grenoble Alpes (UGA), Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Société Francophone de Primatologie, Open Edition, and ANR-18-CE27-0010,HoBiS,Bipédies des Hominines : Analyse de la marche bipède des Hominines par la Morphologie Fonctionnelle Spécimen-Spécifique(2018)
Subjects: Biomécanique, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Forme-fonction, Locomotion
Abstract: Durant la locomotion, la diaphyse fémorale subit des charges mécaniques impactant son organisation structurelle. L’étude de la structure corticale des vestiges fossiles représente donc un potentiel accès à la reconstruction de l’environnement mécanique des hominines fossiles, et donc à leur locomotion. Cependant, peu d’études ont abordé expérimentalement cette question et d’autres facteurs tels que l’âge, la masse et le niveau d’activité viennent complexifier cette relation entre structure fémoro-diaphysaire et locomotion. Une première étude menée sur un échantillon ontogénétique de babouins olive vivant à la Station de Primatologie du CNRS (UAR 846), a démontré une faible correspondance entre les variations de l’organisation du tissu cortical de la diaphyse fémorale et celles du répertoire posturo-locomoteur au cours de l’âge. Pour poursuivre l’étude de cette relation entre les propriétés biomécaniques de la diaphyse fémorale et la locomotion, nous avons analysé et comparé les cartographies d’épaisseur corticale et des paramètres de géométrie de section sur plus de 50 fémurs de primates catarhiniens adultes (genres Homo, Gorilla, Pan, Hylobates, Papio, Macaca), de morphologies et de répertoires posturo-locomoteurs différents.Nos résultats montrent l’existence de schémas biomécaniques variés, montrant une certaine proximité entre grands singes africains et hylobatidés, dont les babouins et surtout les humains se distinguent. Les propriétés biomécaniques de la diaphyse fémorale permettent de distinguer des grands groupes, mais pas de caractériser précisément les répertoires posturo-locomoteurs les plus diversifiés.Pour permettre une différenciation plus fine des répertoires posturo-locomoteurs complexes, exploitable dans une perspective paléoanthropologique, nous proposons l’intégration de l’approche biomécanique à de la morphométrie géométrique.
Published: 2022

7. Different Alterations of Agonist and Antagonist Binding to 5-HT1A Receptor in a Rat Model of Parkinson’s Disease and Levodopa-Induced Dyskinesia: A MicroPET Study

Author: Luc Zimmer, Adrian Newman-Tancredi, Sarah Chaib, Benjamin Vidal, Caroline Bouillot, Thierry Billard, Elise Levigoureux, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Agonist, Dyskinesia, Drug-Induced, medicine.medical_specialty, Parkinson's disease, medicine.drug_class, Stimulation, Serotonin 5-HT1 Receptor Antagonists, Antiparkinson Agents, Levodopa, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, GPCR, 0302 clinical medicine, Dopamine, Internal medicine, medicine, Animals, Levodopa-induced dyskinesia, business.industry, Parkinson Disease, Serotonin 5-HT1 Receptor Agonists, medicine.disease, Rats, serotonin, nervous system diseases, Disease Models, Animal, 030104 developmental biology, Endocrinology, nervous system, chemistry, Dyskinesia, Receptor, Serotonin, 5-HT1A, 5-HT1A receptor, 5-HT1A, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), MPPF, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Background: The gold-standard treatment for Parkinson’s disease is L-DOPA, which in the long term often leads to levodopa-induced dyskinesia. Serotonergic neurons are partially responsible for this, by converting L-DOPA into dopamine leading to its uncontrolled release as a “false neurotransmitter”. The stimulation of 5-HT1A receptors can reduce involuntary movements but this mechanism is poorly understood. Objective: This study aimed to investigate the functionality of 5-HT1A receptors using positron emission tomography in hemiparkinsonian rats with or without dyskinesia induced by 3-weeks daily treatment with L-DOPA. Imaging sessions were performed “off” L-DOPA. Methods: Each rat underwent a positron emission tomography scan with [18F]F13640, a 5-HT1AR agonist which labels receptors in a high affinity state for agonists, or with [18F]MPPF, a 5-HT1AR antagonist which labels all the receptors. Results: There were decreases of [18F]MPPF binding in hemiparkinsonian rats in cortical areas. In dyskinetic animals, changes were slighter but also found in other regions. In hemiparkinsonian rats, [18F]F13640 uptake was decreased bilaterally in the globus pallidus and thalamus. On the non-lesioned side, binding was increased in the insula, the hippocampus and the amygdala. In dyskinetic animals, [18F]F13640 binding was strongly increased in cortical and limbic areas, especially in the non-lesioned side. Conclusion: These data suggest that agonist and antagonist 5-HT1A receptor-binding sites are differently modified in Parkinson’s disease and levodopa-induced dyskinesia. In particular, these observations suggest a substantial involvement of the functional state of 5-HT1AR in levodopa-induced dyskinesia and emphasize the need to characterize this state using agonist radiotracers in physiological and pathological conditions.
Published: 2021

8. Noradrenaline and Movement Initiation Disorders in Parkinson’s Disease: A Pharmacological Functional MRI Study with Clonidine

Author: Marion Criaud, Chloé Laurencin, Alice Poisson, Elise Metereau, Jérôme Redouté, Stéphane Thobois, Philippe Boulinguez, Bénédicte Ballanger, King‘s College London, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Ballanger, Benedicte
Subjects: Parkinson’s disease, movement initiation, akinesia, inhibitory control, noradrenaline, clonidine, α2-adrenoceptor, functional MRI, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Movement, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Parkinson Disease, General Medicine, Movement Initiation, Magnetic Resonance Imaging, Clonidine, Parkinson’s Disease, Α2-adrenoceptor, Norepinephrine, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Noradrenaline, Inhibitory Control, Humans, Akinesia, Functional MRI
Abstract: International audience; Slowness of movement initiation is a cardinal motor feature of Parkinson’s disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson’s disease
Published: 2022
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9. PET metabolic imaging of time-dependent reorganization of olfactory cued fear memory networks in rats

Author: Anne-Marie Mouly, Philippe Litaudon, Nadine Ravel, Nicolas Costes, Caroline Bouillot, Luc Zimmer, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL), RAVEL, Nadine, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MOULY, Anne-Marie, and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], Hippocampus, Sensory system, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Piriform cortex, Odor, Animals, Fear conditioning, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prefrontal cortex, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Memory Consolidation, Cued speech, 0303 health sciences, Recall, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Fear, Cued Fear conditioning, Recent memory, Odor fear conditioning, Rats, [SDV] Life Sciences [q-bio], [18F]FDG micro PET, Positron-Emission Tomography, Mental Recall, Memory consolidation, System-level consolidation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Remote memory, Cues, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Memory consolidation involves reorganization at both the synaptic and system levels. The latter involves gradual reorganization of the brain regions that support memory and has been mostly highlighted using hippocampal-dependent tasks. The standard memory consolidation model posits that the hippocampus becomes gradually less important over time in favor of neocortical regions. In contrast, this reorganization of circuits in amygdala-dependent tasks has been less investigated. Moreover, this question has been addressed using primarily lesion or cellular imaging approaches thus precluding the comparison of recent and remote memory networks in the same animals. To overcome this limitation, we used microPET imaging to characterize, in the same animals, the networks activated during the recall of a recent versus remote memory in an olfactory cued fear conditioning paradigm. The data highlighted the drastic difference between the extents of the two networks. Indeed, although the recall of a recent odor fear memory activates a large network of structures spanning from the prefrontal cortex to the cerebellum, significant activations during remote memory retrieval are limited to the piriform cortex. These results strongly support the view that amygdala-dependent memories also undergo system-level reorganization, and that sensory cortical areas might participate in the long-term storage of emotional memories.
Published: 2022

10. Study of Carbamoyl Fluoride: Synthesis, Properties and Applications

Author: Clémence Bonnefoy, Emmanuel Chefdeville, Christian Tourvieille, Armen Panossian, Gilles Hanquet, Frédéric Leroux, Fabien Toulgoat, Thierry Billard, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire d'innovation moléculaire et applications (LIMA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Billard, Thierry
Subjects: Fluorides, Fluorine Radioisotopes, Radiochemistry, Halogenation, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, General Chemistry, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Catalysis
Abstract: International audience; Carbamoyl fluoride is a fluorinated group which, to this date, remains underexplored, probably due to the lack of data concerning their properties. In this paper, a study of carbamoyl fluoride is proposed. Stability studies, in particular under physiological conditions, and lipophilicity measurement have been performed. A new easy, safe, inexpensive and metal-free synthesis method has also been described. Finally, a potential use in radiochemistry through a 18 F/ 19 F isotopic exchange has been demonstrated.
Published: 2022

11. (Trifluoromethylselenyl)methylchalcogenyl as Emerging Fluorinated Groups: Synthesis under Photoredox Catalysis and Determination of the Lipophilicity

Author: Kevin Grollier, Arnaud De Zordo-Banliat, Flavien Bourdreux, Guillaume Dagousset, Emmanuel Magnier, Thierry Billard, Bruce Pégot, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and ANR-18-CE07-0039,SAFA,Selenium et Fluor Associés: le mariage de 2 stars(2018)
Subjects: Molecular Structure, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, Decarboxylation, Organic Chemistry, Photoredox catalysis, chemistry.chemical_element, General Chemistry, Flow chemistry, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, Catalysis, 0104 chemical sciences, Lipophilicity, Fluorine, [CHIM]Chemical Sciences, Molecule, Surface modification, Oxidation-Reduction
Abstract: International audience; The synthesis of molecules bearing (trifluoromethylselenyl)methylchalcogenyl groups is described via an efficient two-step strategy based on a metal-free photoredox catalyzed decarboxylative trifluoromethylselenolation with good yields up to 88% which raised to 98% in flow chemistry conditions. The flow methods allowed also to scale up the reaction. The mechanism of this key reaction was studied. The physico-chemical characterization of these emerging groups was performed by determining their Hansch-Leo lipophilicity parameters with high values up to 2.24. This reaction was also extended to perfluoroalkylselenolation with yields up to 95%. Finally, this method was successfully applied to the functionalization of relevant bioactive molecules such as tocopherol or estrone derivatives.
Published: 2021

12. Innovative approaches in CNS drug discovery

Author: Luc Zimmer, Mathieu Charvériat, Vincent Lafon, Franck Mouthon, Theranexus [Lyon], Insiliance, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Big Data, medicine.medical_specialty, Neurology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Big data, 030226 pharmacology & pharmacy, 03 medical and health sciences, Neuropharmacology, 0302 clinical medicine, Artificial Intelligence, medicine, Animals, Humans, Pharmacology (medical), Intensive care medicine, Drug discovery, business.industry, Translational, Biomarker, 3. Good health, Central nervous system, Therapeutic Area, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Central Nervous System Agents
Abstract: International audience; Central nervous system disorders remain the leading causes of mortality and morbidity worldwide, affecting more than 1 billion patients. This therapeutic area suffers from high unmet medical needs and the search for innovative approaches to identify therapeutic strategies is urgent in the field. This review will first cover the challenges and opportunities of drug discovery in neurology, and then as well as the new models, such as human model stem cells and animal models under development in the field. In addition, innovative and translational neuroimaging techniques will be discussed, as the use of big data and artificial intelligence to discovery new drugs in neurological and neuropsychiatric disorders.
Published: 2021

13. Towards in vivo imaging of functionally active 5-HT1A receptors in schizophrenia: concepts and challenges

Author: Adrian Newman-Tancredi, Luc Zimmer, Oriane Razakarivony, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Neurolixis, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Rayet, Béatrice, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Agonist, medicine.drug_class, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neuroimaging, medicine, Radioligand, Receptor, Antipsychotic, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Schizophrenia, Serotonin, business, Neuroscience, 030217 neurology & neurosurgery, Preclinical imaging, Biomarkers
Abstract: The serotonin 5-HT1A receptor has attracted wide attention as a target for treatment of psychiatric disorders. Although this receptor is important in the pharmacological mechanisms of action of new-generation antipsychotics, its characterization remains incomplete. Studies based on in vitro molecular imaging on brain tissue by autoradiography, and more recently in vivo PET imaging, have not yielded clear results, in particular due to the limitations of current 5-HT1A radiotracers, which lack specificity and/or bind to all 5-HT1A receptors, regardless of their functional status. The new concept of PET neuroimaging of functionally active G-protein-coupled receptors makes it possible to revisit PET brain exploration by enabling new research paradigms. For the 5-HT1A receptor it is now possible to use [18F]-F13640, a 5-HT1A receptor radioligand with high efficacy agonist properties, to specifically visualize and quantify functionally active receptors, and to relate this information to subjects’ pathophysiological or pharmacological state. We therefore propose imaging protocols to follow changes in the pattern of functional 5-HT1A receptors in relation to mood deficits or cognitive processes. This could allow improved discrimination of different schizophrenia phenotypes and greater understanding of the basis of therapeutic responses to antipsychotic drugs. Finally, as well as targeting functionally active receptors to gain insights into the role of 5-HT1A receptors, the concept can also be extended to the study of other receptors involved in the pathophysiology or therapy of psychiatric disorders.
Published: 2021

14. Reassessment of mitochondrial cyclophilin D as a target for improving cardiac arrest outcomes in the era of therapeutic hypothermia

Author: VINCENT Jahandiez, BRUNO PILLOT, GABRIEL BIDAUX, RADU BOLBOS, NEVEN STEVIC, MARLENE WIART, MICHEL OVIZE, LAURENT ARGAUD, MARTIN COUR, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Wiart, Marlene
Subjects: Mice, Knockout, Biochemistry (medical), Public Health, Environmental and Occupational Health, General Medicine, Hypothermia, Troponin, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Heart Arrest, Mice, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Hypothermia, Induced, Physiology (medical), [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cyclosporine, Animals, Biomarkers, Cyclophilin D
Abstract: International audience; Uncertainty exists regarding whether cyclophilin D (CypD), a mitochondrial matrix protein that plays a key role in ischemia-reperfusion injury, can be a pharmacological target for improving outcomes after cardiac arrest (CA), especially when therapeutic hypothermia is used. Using CypD knockout mice (CypD−/−), we investigated the effects of loss of CypD on short-term and medium-term outcomes after CA. CypD−/− mice or their wild-type (WT) littermates underwent either 5-minute CA followed by resuscitation with/without hypothermia at 33-34 C (targeted temperature reached within minutes after resuscitation), or a sham procedure. Brain and cardiac injury were assessed using echocardiography, neurological scores, MRI and biomarkers. Seven-day survival was compared using Kaplan-Meier estimates. The rate of restoration of spontaneous circulation was significantly higher in CypD−/− mice (with shorter cardiac massage duration) than in WT mice (p
Published: 2022

15. Evaluation of markerless prospective motion correction for neuroanatomical MRI

Author: Zariry, Zakaria, Frost, Robert, Lamberton, Franck, Troalen, Thomas, Richard, Nathalie, van der Kouwe, Andre, Hiba, Bassem, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Siemens Healthcare [France], Siemens AG [Munich], and HIBA, Bassem
Subjects: [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging
Abstract: International audience; Head-motion is a main cause of artifacts in MRI. The performance of a markerless optical system, which records the subject's face, estimates head-motion, and allows real-time repositioning of the FOV, is evaluated for neuroanatomical MRI. Sets of T1W/T2W-images were collected from 2 subjects instructed to perform different head-motion protocols during the acquisitions. The System performance is evaluated by comparing images with/without motion-correction. The optical system ensures good corrections of head-motions. However, the correction quality depends on the amplitude of the movement, its location in k-space and its nature. Residual effects of large amplitudes/amounts movements may persist on corrected images. Summary of main findings:-Good performance of prospective motion correction for anatomical brain MRI-Correction quality depends on the magnitude of the motion, its location in k-space and its nature-Optical system is more effective at correcting discontinuous than continuous large motions, especially for T2W-MRI
Published: 2022

16. A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

Author: F. Taborik, Karine Portier, Norbert Nighoghossian, Adrien Oudotte, Michaël Verset, Thomas Troalen, Omer Eker, Denis Vivien, Inés Mérida, Christelle Leon, Christian Tourvieille, Didier Le Bars, Emmanuelle Canet-Soulas, Michel Ovize, Hugues Contamin, Nicolas Costes, Nikolaos Makris, Véronique Agin, Joachim Confais, Tae-Hee Cho, Mohamed Aggour, Sophie Lancelot, Justine Debatisse, Jean-Baptiste Langlois, Océane Wateau, Marjorie Villien, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), Cynbiose, CYNBIOSE, Institut Claude Bourgelat (ICLB), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Siemens Healthcare [France], Siemens AG [Munich], Institute of Electronic Structure and Laser (FORTH-IESL), Foundation for Research and Technology - Hellas (FORTH), Radiopharmaceutical and Neurochemical Biomarkers Team (BioRaN), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Cardiology, Hospices Civils de Lyon (HCL), Laboratoire de Chimie de la Matière Condensée de Paris (site ENSCP) (LCMCP (site ENSCP)), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), French Ministry of Higher Education and Research (ANRT), ANR-15-CE17-0020,CYCLOPS,CYCLOsporine A : effet neuroprotecteur dans un modèle Primate de Stroke en imagerie(2015), ANR-16-RHUS-0009,MARVELOUS,MARVELOUS(2016), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV]Life Sciences [q-bio], Executive Function, 0302 clinical medicine, Occlusion, Stroke, Thrombectomy, 0303 health sciences, Behavior, Animal, Endovascular Procedures, Infarction, Middle Cerebral Artery, Magnetic Resonance Imaging, 3. Good health, Treatment Outcome, Neurology, Blood-Brain Barrier, Motor Skills, Reperfusion Injury, Middle cerebral artery, Cardiology, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Ischemia, Context (language use), ischemia–reperfusion, Asymptomatic, Lesion, 03 medical and health sciences, medicine.artery, Internal medicine, medicine, Animals, cardiovascular diseases, Thrombus, Ischemic Stroke, 030304 developmental biology, business.industry, Original Articles, medicine.disease, Disease Models, Animal, Macaca fascicularis, Endovascular non-human primate stroke model, PET-MRI imaging, Positron-Emission Tomography, neurofunctional tests, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract: International audience; Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.
Published: 2020

17. Widening of the genetic and clinical spectrum of Lamb-Shaffer syndrome, a neurodevelopmental disorder due to SOX5 haploinsufficiency

Author: Ashley N. Sigafoos, Salima El Chehadeh, Marcia C. Willing, Ela Akay, Florian Cherik, Anne-Marie E. Goyette, Vinodh Narayanan, Diane Masser-Frye, Catherine Karimov, Rhonda E. Schnur, Rebekah Bressi, Rhys H. Thomas, Gary D. Clark, Tina Barbaro-Dieber, Jill A. Rosenfeld, Carlos A. Bacino, Maria J. Guillen Sacoto, Laura Russell, Kristin Lindstrom, Caroline Schluth-Bolard, Xia Wang, Yvonne Hilhorst-Hofstee, Marcelo Vargas, Zehua Zhu, Ash Zawerton, Boris Keren, Mariëtte J.V. Hoffer, Isabelle Marey, Alice Poisson, Daphné Lehalle, Maries Joseph, Gaetan Lesca, Simon Zwolinski, Laurence Perrin, Rhoda Akilapa, Emilia K. Bijlsma, Christel Depienne, Amélie Piton, Claire G. Salter, Lucie Dupuis, Daryl A. Scott, Jolien S. Klein Wassink-Ruiter, Benjamin Cogné, Mathilde Nizon, Richard Chang, Kirsty McWalter, Myriam Srour, Perrine Charles, Anne-Claude Tabet, Natalie Canham, Sylvie Odent, Caroline Nava, Karl J. Clark, Elizabeth J. Bhoj, Jonathan Levy, Keri Ramsey, Yves Alembik, Lucia Ortega, Sophie Dupuis-Girod, Shoji Ichikawa, Christine Francannet, Marta Bertoli, Christèle Dubourg, Eric W. Klee, Ange-Line Bruel, Sebastien Moutton, Emily Fassi, Anthony Vandersteen, Abdul Haseeb, Antonina Wojcik, Patrick R. Blackburn, Lynne M. Bird, Patrick Rump, Véronique Lefebvre, Alma Kuechler, Sophie Nambot, Keren Machol, Cyril Mignot, Andreas Hartmann, Rossana Sanchez Russo, Erica H. Gerkes, Sylvie Jaillard, Roberto Mendoza-Londono, Trevor Cole, Pauline Monin, Cleveland Clinic, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Center for Human and Clinical Genetics, Leiden University Medical Center (LUMC), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, This research was funded in part by the Agence Nationale de la Recherche and European High-Functioning Autism Network (ANR EUHFAUTISM), the Assistance Publique–Hôpitaux de Paris (AP-HP), the Institut National de la Santé et de la Recherche Médicale (INSERM), the BioPsy labex (to Christel Depienne and C.N.) and the Association Française du Syndrome Gilles de la Tourette (AFSGT) to Christel Depienne. It was also funded by the Cleveland Clinic Lerner Research Institute (LRI Chair’s Innovative Research Award to V.L.), and by Harper’s Quest and the LAMSHF Syndrome Research Fund (donations to V.L.) and the Center for Individualized Medicine, Mayo Clinic. This study makes use of data generated by the DECIPHER community and the Deciphering Developmental Disorders (DDD) Study, which is funded by the Wellcome Trust. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network., We thank the patients and their families for their participation in this study, and the C4RCD Research Group (Newell Belnap, Amanda Courtright, Ana Claasen, David Craig, Matt Huentelman, Madison LaFleur, Sampathkumar Rangasamy, Ryan Richholt, Isabelle Schrauwen, Ashley L. Siniard, and Szabolics Szelinger) for providing clinical information on patient P18., Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Centre d'Exploration et de Recherche Médicales par Émission de Positons (CERMEP), Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Medizin, Haploinsufficiency, L-SOX5, VARIANTS, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, Missense mutation, 2.1 Biological and endogenous factors, Aetiology, Child, Genetics (clinical), Genetics, Pediatric, Genetics & Heredity, 0303 health sciences, Pedigree, FAMILY, DNA-Binding Proteins, developmental delay, TRANSCRIPTION FACTORS, Phenotype, intellectual disability, Child, Preschool, missense variants, Female, SOXD Transcription Factors, Adult, EXPRESSION, Adolescent, Intellectual and Developmental Disabilities (IDD), Clinical Sciences, Mutation, Missense, autism, Cell fate determination, Biology, LONG FORM, SEQUENCE, Article, 03 medical and health sciences, Young Adult, Rare Diseases, Clinical Research, CARTILAGE, Intellectual Disability, medicine, Animals, Humans, Language Development Disorders, Genetic Predisposition to Disease, Preschool, Transcription factor, Gene, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MUTATIONS, Human Genome, Infant, medicine.disease, Brain Disorders, Neurodevelopmental Disorders, Deciphering Developmental Disorder Study, Mutation, Autism, epilepsy, Missense, 030217 neurology & neurosurgery, GENERATION
Abstract: International audience; PURPOSE: Lamb-Shaffer syndrome (LAMSHF) is a neurodevelopmental disorder described in just over two dozen patients with heterozygous genetic alterations involving SOX5, a gene encoding a transcription factor regulating cell fate and differentiation in neurogenesis and other discrete developmental processes. The genetic alterations described so far are mainly microdeletions. The present study was aimed at increasing our understanding of LAMSHF, its clinical and genetic spectrum, and the pathophysiological mechanisms involved.METHODS: Clinical and genetic data were collected through GeneMatcher and clinical or genetic networks for 41 novel patients harboring various types of SOX5 alterations. Functional consequences of selected substitutions were investigated.RESULTS: Microdeletions and truncating variants occurred throughout SOX5. In contrast, most missense variants clustered in the pivotal SOX-specific high-mobility-group domain. The latter variants prevented SOX5 from binding DNA and promoting transactivation in vitro, whereas missense variants located outside the high-mobility-group domain did not. Clinical manifestations and severity varied among patients. No clear genotype-phenotype correlations were found, except that missense variants outside the high-mobility-group domain were generally better tolerated.CONCLUSIONS:This study extends the clinical and genetic spectrum associated with LAMSHF and consolidates evidence that SOX5 haploinsufficiency leads to variable degrees of intellectual disability, language delay, and other clinical features.
Published: 2020

18. Inhibition of alkaline phosphatase impairs dyslipidemia and protects mice from atherosclerosis

Author: Laurence Bessueille, Lynn Kawtharany, Thibaut Quillard, Claudia Goettsch, Anne Briolay, Nirina Taraconat, Stéphane Balayssac, Véronique Gilard, Saida Mebarek, Olivier Peyruchaud, François Duboeuf, Caroline Bouillot, Anthony Pinkerton, Laura Mechtouff, René Buchet, Eva Hamade, Kazem Zibara, Caroline Fonta, Emmanuelle Canet-soulas, Jose luis Millan, David Magne, Fonta, Caroline, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Sanford Burnham Prebys Medical Discovery Institute, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lebanese University [Beirut] (LU), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), BIBAC - Chimie analytique et interactions biomolécules - matière molle biomimétique (BIBAC), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
Subjects: calcification, inflammation, Physiology (medical), Biochemistry (medical), Public Health, Environmental and Occupational Health, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, General Medicine, TNAP, liver, metabolic syndrome
Abstract: International audience; Calcium accumulation in atherosclerotic plaques predicts cardiovascular mortality, but the mechanisms responsible for plaque calcification and how calcification impacts plaque stability remain debated. Tissue-nonspecific alkaline phosphatase (TNAP) recently emerged as a promising therapeutic target to block cardiovascular calcification. In this study, we sought to investigate the effect of the recently developed TNAP inhibitor SBI-425 on atherosclerosis plaque calcification and progression. TNAP levels were investigated in ApoE-deficient mice fed a high-fat diet from 10 weeks of age and in plaques from the human ECLAGEN biocollection (101 calcified and 14 non-calcified carotid plaques). TNAP was inhibited in mice using SBI-425 administered from 10 to 25 weeks of age, and in human vascular smooth muscle cells (VSMCs) with MLS-0038949. Plaque calcification was imaged in vivo with 18F-NaF-PET/CT, ex vivo with osteosense, and in vitro with alizarin red. Bone architecture was determined with µCT. TNAP activation preceded and predicted calcification in human and mouse plaques, and TNAP inhibition prevented calcification in human VSMCs and in ApoE-deficient mice. More unexpectedly, TNAP inhibition reduced the blood levels of cholesterol and triglycerides, and protected mice from atherosclerosis, without impacting the skeletal architecture. Metabolomics analysis of liver extracts identified phosphocholine as a substrate of liver TNAP, who's decreased dephosphorylation upon TNAP inhibition likely reduced the release of cholesterol and triglycerides into the blood. Systemic inhibition of TNAP protects from atherosclerosis, by ameliorating dyslipidemia, and preventing plaque calcification.
Published: 2022

19. Neurofunctional and neuroimaging readouts for designing a preclinical stem-cell therapy trial in experimental stroke

Author: Camille Amaz, Marlène Wiart, Chrystelle Po, Claire Rome, Matthieu Chourrout, Chloé Dumot, Céline Auxenfans, Radu Bolbos, Elodie Ong, Emmanuelle Canet-Soulas, Fabien Chauveau, Violaine Hubert, Lucille Capin, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CIC CHU Lyon (inserm), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-18-CE19-0003,BREAKTHRU,Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires(2018), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Wiart, Marlene, and APPEL À PROJETS GÉNÉRIQUE 2018 - Développement de l'imagerie bicolore à l'aide d'un scanner X spectral à comptage de photons pour l'évaluation in-vivo de thérapies cellulaires - - BREAKTHRU2018 - ANR-18-CE19-0003 - AAPG2018 - VALID
Subjects: [SDV.IB] Life Sciences [q-bio]/Bioengineering, Multidisciplinary, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Cell- and Tissue-Based Therapy, Stem-cell therapy, medicine.disease, Rats, 3. Good health, Stroke, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Neuroimaging, nervous system, medicine, Animals, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Neuroscience, Ischemic Stroke
Abstract: With the aim of designing a preclinical study evaluating an intracerebral cell-based therapy for stroke, an observational study was performed in the rat suture model of ischemic stroke. Objectives were threefold: (i) to characterize neurofunctional and imaging readouts in the first weeks following transient ischemic stroke, according to lesion subtype (hypothalamic, striatal, corticostriatal); (ii) to confirm that intracerebral administration does not negatively impact these readouts; and (iii) to calculate sample sizes for a future therapeutic trial using these readouts as endpoints. Our results suggested that the most relevant endpoints were side bias (staircase test) and axial diffusivity (AD) (diffusion tensor imaging). Hypothalamic-only lesions did not affect those parameters, which were close to normal. Side bias in striatal lesions reached near-normal levels within 2 weeks, while rats with corticostriatal lesions remained impaired until week 14. AD values were decreased at 4 days and increased at 5 weeks post-surgery, with a subtype gradient: hypothalamic < striatal < corticostriatal. Intracerebral administration did not impact these readouts. After sample size calculation (18-147 rats per group according to the endpoint considered), we conclude that a therapeutic trial based on both readouts would be feasible only in the framework of a multicenter trial.
Published: 2021

20. Solvent free nucleophilic selenocyanation with [bmim][SeCN]. Direct access to perfluoroalkylselenide compounds

Author: Emmanuel Magnier, Guillaume Dagousset, Arnaud De-Zordo Banliat, Aurélie Damond, Thierry Billard, Kevin Grollier, Bruce Pégot, Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and ANR-18-CE07-0039,SAFA,Selenium et Fluor Associés: le mariage de 2 stars(2018)
Subjects: chemistry.chemical_classification, Solvent free, 010405 organic chemistry, Organic Chemistry, Two step, Halide, 010402 general chemistry, Selenocyanation, 01 natural sciences, Biochemistry, 6. Clean water, 0104 chemical sciences, Ionic liquids, chemistry.chemical_compound, Nucleophilic substitution, Nucleophile, chemistry, Green chemistry, Reagent, Drug Discovery, Polymer chemistry, Ionic liquid, [CHIM]Chemical Sciences, Microwaves, Alkyl
Abstract: International audience; Available online-1-n-butyl-3-methylimidazolium selenocyanate ([bmim][SeCN]) proved to be a very efficient reagent for selenocyanation of alkyl halides. As part of an eco-friendly process, no organic solvents were used during the transformation and reaction times are reduced by using microwave as a heating source. The ionic liquid was carefully recycled in two different ways. Selenocyanate compounds were successfully transformed into trifluoromethylselenides in a one-pot two step procedure.
Published: 2021

21. The cortical thickness of the area PF of the left inferior parietal cortex mediates technical-reasoning skills

Author: Federico, Giovanni, Reynaud, Emanuelle, Navarro, Jordan, Lesourd, Mathieu, Gaujoux, Vivien, Lamberton, Franck, Ibarrola, Danièle, Cavaliere, Carlo, Alfano, Vincenzo, Aiello, Marco, Salvatore, Marco, Seguin, Perrine, Schnebelen, Damien, Brandimonte, Maria, Rossetti, Yves, Osiurak, François, Osiurak, François, SDN - Istituto di Ricerca Diagnostica e Nucleare, Laboratoire d'Etude des Mécanismes Cognitifs (EMC), Université Lumière - Lyon 2 (UL2), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Maison des Sciences de l'Homme et de l'Environnement Claude Nicolas Ledoux (UAR 3124) (MSHE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Santé Lyon Est - Louis Léopold Ollier, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi Suor Orsola Benincasa (UNISOB), Hospices Civils de Lyon (HCL), Hôpital Henry Gabrielle [CHU - HCL], Institut Universitaire de France (IUF), and Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Subjects: Thinking, Technology, Parietal Lobe, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Brain, Humans, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Problem Solving
Abstract: International audience; Most recent research highlights how a specific form of causal understanding, namely technical reasoning, may support the increasing complexity of tools and techniques developed by humans over generations, i.e., the cumulative technological culture (CTC). Thus, investigating the neurocognitive foundations of technical reasoning is essential to comprehend the emergence of CTC in our lineage. Whereas functional neuroimaging evidence started to highlight the critical role of the area PF of the left inferior parietal cortex (IPC) in technical reasoning, no studies explored the links between the structural characteristics of such a brain region and technical reasoning skills. Therefore, in this study, we assessed participants’ technical-reasoning performance by using two ad-hoc psycho-technical tests; then, we extracted from participants’ 3 T T1-weighted magnetic-resonance brain images the cortical thickness (i.e., a volume-related measure which is associated with cognitive performance as reflecting the size, density, and arrangement of cells in a brain region) of all the IPC regions for both hemispheres. We found that the cortical thickness of the left area PF predicts participants’ technical-reasoning performance. Crucially, we reported no correlations between technical reasoning and the other IPC regions, possibly suggesting the specificity of the left area PF in generating technical knowledge. We discuss these findings from an evolutionary perspective, by speculating about how the evolution of parietal lobes may have supported the emergence of technical reasoning in our lineage.
Published: 2021

22. Modeling [11C]yohimbine PET human brain kinetics with test-retest reliability, competition sensitivity studies and search for a suitable reference region

Author: Laurencin, Chloé, Lancelot, Sophie, Gobert, Florent, Redouté, Jérôme, Mérida, Inés, Iecker, Thibault, Liger, François, Irace, Zacharie, Greusard, Elise, Lamberet, Ludovic, Bars, Didier, Costes, Nicolas, Ballanger, Bénédicte, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Siemens Healthcare, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), ANR-16-CE37-0014,INSyst,Etude du système noradrénergique in vivo chez l'homme par imagerie hybride moléculaire/fonctionnelle(2016), Ballanger, Benedicte, and Etude du système noradrénergique in vivo chez l'homme par imagerie hybride moléculaire/fonctionnelle - - INSyst2016 - ANR-16-CE37-0014 - AAPG2016 - VALID
Subjects: [SDV] Life Sciences [q-bio], Positron emission tomography, [SDV]Life Sciences [q-bio], Compartmental modeling, α2-adrenoceptors, Neurosciences. Biological psychiatry. Neuropsychiatry, Human brain, [11C]yohimbine, ComputingMilieux_MISCELLANEOUS, RC321-571
Abstract: Previous work introduced the [11C]yohimbine as a suitable ligand of central α2-adrenoreceptors (α2-ARs) for PET imaging. However, reproducibility of [11C]yohimbine PET measurements in healthy humans estimated with a simplified modeling method with reference region, as well as sensitivity of [11C]yohimbine to noradrenergic competition were not evaluated. The objectives of the present study were therefore to fill this gap. Methods: Thirteen healthy humans underwent two [11C]yohimbine 90-minute dynamic scans performed on a PET-MRI scanner. Seven had arterial blood sampling with metabolite assessment and plasmatic yohimbine free fraction evaluation at the first scan to have arterial input function and test appropriate kinetic modeling. The second scan was a simple retest for 6 subjects to evaluate the test-retest reproducibility. For the remaining 7 subjects the second scan was a challenge study with the administration of a single oral dose of 150 µg of clonidine 90 min before the PET scan. Parametric images of α2-ARs distribution volume ratios (DVR) were generated with two non-invasive models: Logan graphical analysis with Reference (LREF) and Simplified Reference Tissue Method (SRTM). Three reference regions (cerebellum white matter (CERWM), frontal white matter (FLWM), and corpus callosum (CC)) were tested. Results: We showed high test-retest reproducibility of DVR estimation with LREF and SRTM regardless of reference region (CC, CERWM, FLWM). The best fit was obtained with SRTMCC (r2=0.94). Test-retest showed that the SRTMCC is highly reproducible (mean ICC>0.7), with a slight bias (-1.8%), whereas SRTMCERWM had lower bias (-0.1%), and excellent ICC (mean>0.8). Using SRTMCC, regional changes have been observed after clonidine administration with a significant increase reported in the amygdala and striatum as well as in several posterior cortical areas as revealed with the voxel-based analysis. Conclusion: The results add experimental support for the suitability of [11C]yohimbine PET in the quantitative assessment of α2-ARs occupancy in vivo in the human brain.Trial registration EudraCT 2018-000380-82
Published: 2021

23. Rescheduling in textile industry : an unrelated parallel machines problem with setup times

Author: Berthier, Alice, Yalaoui, Alice, Chehade, Hicham, Yalaoui, Farouk, Amodeo, Lionel, Bouillot, C., Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Laboratoire Informatique et Société Numérique (LIST3N), Université de Technologie de Troyes (UTT)-Université de Technologie de Troyes (UTT), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

24. Serotonin 5-HT1A Receptor Biased Agonists Induce Different Cerebral Metabolic Responses: A [18F]-Fluorodesoxyglucose Positron Emission Tomography Study in Conscious and Anesthetized Rats

Author: Stéphane Emery, Sylvain Fieux, Luc Zimmer, Benjamin Vidal, Adrian Newman-Tancredi, Elise Levigoureux, Caroline Bouillot, Radiopharmaceutical and Neurochemical Biomarkers Team (BioRaN), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Neurolixis, and Hospices Civils de Lyon (HCL)
Subjects: positron emission tomography, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Physiology, Cognitive Neuroscience, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Functional selectivity, Receptor, 5-HT receptor, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, Chemistry, Cell Biology, General Medicine, serotonin, biased agonism, Positron emission tomography, 5-HT1A receptor, 5-HT1A receptors, functional selectivity, Serotonin, [18F]FDG, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Serotonin 5-HT1A receptors constitute an attractive therapeutic target for various psychiatric or neurodegenerative disorders. These receptors are expressed in multiple brain regions on different neuronal populations and can be coupled with distinct G-protein subtypes; such functional diversity complicates the use of 5-HT1A ligands in several pathologies where it would be desirable to stimulate the receptors in a precise region. Therefore, using “biased agonists” able to target specifically certain subpopulations of 5-HT1A receptors would enable achievement of better therapeutic benefit. Several 5-HT1A receptor biased agonists are currently in development, including NLX-101 (aka F15599) and NLX-112 (aka F13640, befiradol), with preclinical data suggesting that they preferentially target different populations of 5-HT1A receptors. However, most previous studies used invasive and regionally limited approaches. In this context, [18F]-fluorodesoxyglucose (FDG)-positron emission tomography (PET) imaging constitutes an interesting technique as it enables noninvasive mapping of the regional brain activity changes following a pharmacological challenge in conscious animals. We report here the evaluation of cerebral glucose metabolism following intraperitoneal injection of different doses of NLX-112 or NLX-101 in conscious or isoflurane-anesthetized rats. The biased agonists produced different metabolic “fingerprints” with distinct regional preferences, consistent with previous studies. At equal doses, the effect of NLX-101 was less marked than NLX-112 in the piriform cortex, in the striatum (in terms of inhibition), and in the pontine nuclei and the cerebellum (in terms of activation); furthermore, only NLX-112 increased the glucose metabolism in the parietal cortex, whereas only NLX-101 induced a clear activation in the colliculi and the frontal cortex, which may be related to its distinctive procognitive profile. Both agonist effects were almost completely unapparent in anesthetized animals, underlining the importance of studying serotonergic neurotransmission in the conscious state. In this regard, [18F]FDG-PET imaging seems very complementary with other functional imaging techniques such as pharmacological MRI.
Published: 2018

25. Evaluation of [18 F]2FP3 in pigs and non-human primates

Author: Luc Zimmer, Janus H. Magnussen, Gilles Tamagnan, Matthias M. Herth, Olivier Barret, Agnete Dyssegaard, Szabolcs Lehel, Cristian Constantinescu, Thierry Billard, Gitte M. Knudsen, Julie Colomb, Hanne D. Hansen, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Synthèse, Utilisation, Réactivité des Composés Organiques et OrganoFluorés (SURCOOF), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: 0301 basic medicine, Biochemistry, Analytical Chemistry, 5-HT7 receptor, 03 medical and health sciences, 0302 clinical medicine, In vivo, Drug Discovery, medicine, Radioligand, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, Spectroscopy, CATS, medicine.diagnostic_test, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Chemistry, Organic Chemistry, Antagonist, Human brain, Molecular biology, 3. Good health, High uptake, 030104 developmental biology, medicine.anatomical_structure, Positron emission tomography, 030220 oncology & carcinogenesis
Abstract: So far, no suitable 5-HT7 R radioligand exists for clinical positron emission tomography (PET) imaging. [18 F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7 R binding with [3 H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18 F]2FP3 was investigated by intravenous administration of the 5-HT7 R specific antagonist SB-269970. [3 H]SB-269970 autoradiography was performed as previously described. [18 F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7 R-rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3 H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18 F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7 Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7 R.
Published: 2018

26. Variation in the sacroiliac joint in Felidae

Author: Mélina Ribaud, Eric Pellé, Grégory Breton, Vincent Bels, Jean-Pierre Pallandre, Franck Lavenne, Gestionnaire, HAL Sorbonne Université 5, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut des sciences biologiques (INSB-CNRS), Muséum national d'Histoire naturelle (MNHN), Panthera, Biostatistique et Processus Spatiaux (BioSP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and INSB
Subjects: 0106 biological sciences, Arboreal locomotion, Felidae, Evolution, Foraging, Zoology, 010603 evolutionary biology, 01 natural sciences, Cursorial, Sacroiliac junction, General Biochemistry, Genetics and Molecular Biology, Predation, Pelvis, Ilium, 03 medical and health sciences, biology.animal, Acinonyx jubatus, Leopardus wiedii, 030304 developmental biology, 0303 health sciences, biology, General Neuroscience, Felis, General Medicine, 15. Life on land, Predatory behavior, biology.organism_classification, Evolutionary Studies, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Medicine, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Panthera, General Agricultural and Biological Sciences, Locomotion
Abstract: Felidae species show a great diversity in their diet, foraging and hunting strategies, from small to large prey. Whether they belong to solitary or group hunters, the behavior of cats to subdue resisting small or large prey presents crucial differences. It is assumed that pack hunting reduces the per capita risk of each individual. We hypothesize that the sacroiliac articulation plays a key role in stabilizing the predator while subduing and killing prey. Using CT-scan from 59 felid coxal bones, we calculated the angle between both iliac articular surfaces. Correlation of this inter-iliac angle with body size was calculated and ecological stressors were evaluated on inter-iliac angle. Body size significantly influences inter-iliac angle with small cats having a wider angle than big cats. Arboreal species have a significantly larger angle compared to cursorial felids with the smallest value, and to scansorial and terrestrial species with intermediate angles. Felids hunting large prey have a smaller angle than felids hunting small and mixed prey. Within the Panthera lineage, pack hunters (lions) have a larger angle than all other species using solitary hunting strategy. According to the inter-iliac angle, two main groups of felids are determined: (i) predators with an angle of around 40° include small cats (i.e., Felis silvestris, Leopardus wiedii, Leptailurus serval, Lynx Canadensis, L. rufus; median = 43.45°), the only pack-hunting species (i.e., Panthera leo; median = 37.90°), and arboreal cats (i.e., L. wiedii, Neofelis nebulosa; median = 49.05°), (ii) predators with an angle of around 30° include solitary-hunting big cats (i.e., Acinonyx jubatus, P. onca, P. pardus, P. tigris, P. uncia; median = 31.80°). We suggest different pressures of selection to interpret these results. The tightening of the iliac wings around the sacrum probably enhances big cats’ ability for high speed and large prey control. In contrast, pack hunting in lions reduced the selective pressure for large prey.
Published: 2021

27. Cortical inflammation and brain signs of high-risk atherosclerosis in a non-human primate model

Author: Cataldo, Vanessa, Debatisse, Justine, Piraquive, Joao, Géloën, Alain, Grandin, Clément, Verset, Michaël, Taborik, Fabrice, Labaronne, Emmanuel, Loizon, Emmanuelle, Millon, Antoine, Mury, Pauline, Pialoux, Vincent, Serusclat, André, Lamberton, Franck, Ibarrola, Danielle, Lavenne, Franck, Le Bars, Didier, Troalen, Thomas, Confais, Joachim, CROLA DA SILVA, Claire, Mechtouff, Laura, Contamin, Hugues, Fayad, Zahi, Canet-Soulas, Emmanuelle, Canet-Soulas, Emmanuelle, MARVELOUS - - MARVELOUS2016 - ANR-16-RHUS-0009 - RHUS - VALID, Equipements d'excellence - Lyon - Imagerie Intégrée du Vivant : IRM-TEP hybride - - LILI2011 - ANR-11-EQPX-0026 - EQPX - VALID, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Siemens Healthcare, CYNBIOSE SA, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Hospices Civils de Lyon (HCL), CERMEP - Imagerie du vivant, Hospices Civils de Lyon, Departement de Neurologie (HCL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), ANR-16-RHUS-0009,MARVELOUS,MARVELOUS(2016), ANR-11-EQPX-0026,LILI,Lyon - Imagerie Intégrée du Vivant : IRM-TEP hybride(2011), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)
Subjects: choroid plexus, AcademicSubjects/SCI01870, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, aging, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Original Article, AcademicSubjects/MED00310, atherosclerosis, stroke, neuroinflammation
Abstract: Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood−brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood−brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy., Elevated cortical inflammation and defective choroid plexus activity associate with high-risk atherosclerosis in cynomolgus monkeys. Using diet-induced atherosclerosis, in-vivo imaging and gene analysis, Di Cataldo et al. showed (i) monkeys exhibit similar atherosclerosis features and vulnerable plaques-associated genes as patients, (ii) brain imaging demonstrated frontal cortex neuroinflammation and neurovascular signs., Graphical Abstract Graphical Abstract
Published: 2021

28. Brain virtual histology with X-ray phase-contrast tomography Part I: whole-brain myelin mapping in white-matter injury models

Author: Chourrout, Matthieu, Rositi, Hugo, Ong, Elodie, Hubert, Violaine, Paccalet, Alexandre, Foucault, Louis, Autret, Awen, Fayard, Barbara, Olivier, Cécile, Bolbos, Radu, Peyrin, Françoise, Crola-Da-Silva, Claire, Meyronet, David, Raineteau, Olivier, Elleaume, Hélène, Brun, Emmanuel, Chauveau, Fabien, Wiart, Marlène, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (U1208 Inserm - UCBL1 / SBRI - USC 1361 INRAE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Novitom [Grenoble], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL), Université de Lyon, Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Imagerie Tomographique et Radiothérapie, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), ANR-15-CE18-0026,NanoBrain,Imagerie de l'inflammation cérébrale dans l'AVC ischémique : développement d'une sonde nanoparticulaire multimodale & méthodes d'imagerie cérébrale(2015), Centre de recherche en neurosciences de Lyon (CRNL), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
Subjects: 0303 health sciences, Pathology, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, business.industry, Multiple sclerosis, White Matter Injury, Tissue Processing, Histology, Human brain, medicine.disease, Article, 03 medical and health sciences, Myelin, 0302 clinical medicine, medicine.anatomical_structure, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Tomography, business, 030217 neurology & neurosurgery, 030304 developmental biology, Diffusion MRI
Abstract: White-matter injury leads to severe functional loss in many neurological diseases. Myelin staining on histological samples is the most common technique to investigate white-matter fibers. However, tissue processing and sectioning may affect the reliability of 3D volumetric assessments. The purpose of this study was to propose an approach that enables myelin fibers to be mapped in the whole rodent brain with microscopic resolution and without the need for strenuous staining. With this aim, we coupled inline (propagation-based) X-ray phase-contrast tomography (XPCT) to ethanol-induced brain sample dehydration. We here provide the proof-of-concept that this approach enhances myelinated axons in rodent and human brain tissue. In addition, we demonstrated that white-matter injuries could be detected and quantified with this approach, using three animal models: ischemic stroke, premature birth and multiple sclerosis. Furthermore, in analogy to diffusion tensor imaging (DTI), we retrieved fiber directions and DTI-like diffusion metrics from our XPCT data to quantitatively characterize white-matter microstructure. Finally, we showed that this non-destructive approach was compatible with subsequent complementary brain sample analysis by conventional histology. In-line XPCT might thus become a novel gold-standard for investigating white-matter injury in the intact brain. This is Part I of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part II shows how in-line XPCT enables the whole-brain 3D morphometric analysis of amyloid-β (Aβ) plaques.HighlightsX-ray phase-contrast tomography (XPCT) enables myelin mapping of the whole brainXPCT detects and quantifies white-matter injuries in a range of diseasesFiber directions and anisotropy metrics can be retrieved from XPCT dataXPCT is compatible with subsequent conventional histology of brain samplesXPCT is a powerful virtual histology tool that requires minimal sample preparationGraphical Abstract
Published: 2021

29. [18F]F13640, a 5-HT1A Receptor Radiopharmaceutical Sensitive to Brain Serotonin Fluctuations

Author: Matthieu Colom, Benjamin Vidal, Sylvain Fieux, Jérôme Redoute, Nicolas Costes, Franck Lavenne, Inés Mérida, Zacharie Irace, Thibaud Iecker, Caroline Bouillot, Thierry Billard, Adrian Newman-Tancredi, Luc Zimmer, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences et Techniques Nucléaires (INSTN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Agonist, Serotonin release, medicine.drug_class, Fenfluramine, serotonin release, [18F]F13640, PET imaging, lcsh:RC321-571, 03 medical and health sciences, [ 18 F]F13640, 0302 clinical medicine, Neuroimaging, medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, agonist, business.industry, General Neuroscience, Pet imaging, 030104 developmental biology, 5-HT 1A receptors, 5-HT1A receptor, 5-HT1A receptors, fenfluramine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Serotonin, business, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: IntroductionSerotonin is involved in a variety of physiological functions and brain disorders. In this context, efforts have been made to investigate the in vivo fluctuations of this neurotransmitter using positron emission tomography (PET) imaging paradigms. Since serotonin is a full agonist, it binds preferentially to G-protein coupled receptors. In contrast, antagonist PET ligands additionally interact with uncoupled receptors. This could explain the lack of sensitivity to serotonin fluctuations of current 5-HT1A radiopharmaceuticals which are mainly antagonists and suggests that agonist radiotracers would be more appropriate to measure changes in neurotransmitter release. The present study evaluated the sensitivity to endogenous serotonin release of a recently developed, selective 5-HT1A receptor PET radiopharmaceutical, the agonist [18F]F13640 (a.k.a. befiradol or NLX-112).Materials and MethodsFour cats each underwent three PET scans with [18F]F13640, i.e., a control PET scan of 90 min, a PET scan preceded 30 min before by an intravenous injection 1 mg/kg of d-fenfluramine, a serotonin releaser (blocking challenge), and a PET scan comprising the intravenous injection of 1 mg/kg of d-fenfluramine 30 min after the radiotracer injection (displacement challenge). Data were analyzed with regions of interest and voxel-based approaches. A lp-ntPET model approach was implemented to determine the dynamic of serotonin release during the challenge study.ResultsD-fenfluramine pretreatment elicited a massive inhibition of [18F]F13640 labeling in regions known to express 5-HT1A receptors, e.g., raphe nuclei, hippocampus, thalamus, anterior cingulate cortex, caudate putamen, occipital, frontal and parietal cortices, and gray matter of cerebellum. Administration of d-fenfluramine during PET acquisition indicates changes in occupancy from 10% (thalamus) to 31% (gray matter of cerebellum) even though the dissociation rate of [18F]F13640 over the 90 min acquisition time was modest. The lp-ntPET simulation succeeded in differentiating the control and challenge conditions.ConclusionThe present findings demonstrate that labeling of 5-HT1A receptors with [18F]F13640 is sensitive to serotonin concentration fluctuations in vivo. Although the data underline the need to perform longer PET scan to ensure accurate measure of displacement, they support clinical development of [18F]F13640 as a tool to explore experimental paradigms involving physiological or pathological (neurological or neuropsychiatric pathologies) fluctuations of extracellular serotonin.
Published: 2021

30. Recent synthetic methods towards the –OCHF2 moiety

Author: Thierry Billard, Anaïs Loison, Frédéric R. Leroux, Fabien Toulgoat, Gilles Hanquet, Armen Panossian, PANOSSIAN, ARMEN, Développement de méthodes de trifluorométhoxylation applicables pour des composés à haute valeur ajoutée et l'imagerie 18F-TEP - - Ap-PET-I2020 - ANR-20-CE07-0004 - AAPG2020 - VALID, Laboratoire d'innovation moléculaire et applications (LIMA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École Supérieure de Chimie Physique Électronique de Lyon (CPE), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and ANR-20-CE07-0004,Ap-PET-I,Développement de méthodes de trifluorométhoxylation applicables pour des composés à haute valeur ajoutée et l'imagerie 18F-TEP(2020)
Subjects: O-Difluoromethylation, Hydrogen bond, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Substituent, chemistry.chemical_element, Fluorine, [CHIM.ORGA] Chemical Sciences/Organic chemistry, Biochemistry, Combinatorial chemistry, Difluoromethoxylation, chemistry.chemical_compound, chemistry, Biological property, Drug Discovery, Moiety, Difluoromethyl ether, Difluoromethyl ester
Abstract: International audience; The fluorine atom and fluorinated substituents are currently key motifs in pharmaceutical and agrochemical active ingredients, since they often beneficially modulate the physico-chemical and biological properties of the latter when installed in place of a hydrogen substituent. Among such fluorinated moieties, –OCHF2 is emerging as an interesting group, which is notably capable of forming a hydrogen bond. These appealing properties have led to a growing need for introduction methods of this group. In this review we summarize all current methods allowing access to the –OCHF2 moiety. We will hence discuss procedures applicable to either aromatic or aliphatic substrates, and based on different disconnections, including difluoromethylation of alcohols, or radical addition onto arenes
Published: 2021

31. Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

Author: Arnaud De Zordo-Banliat, Kevin Grollier, Thierry Billard, Emmanuel Magnier, Alexis Taponard, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and ANR-18-CE07-0039,SAFA,Selenium et Fluor Associés: le mariage de 2 stars(2018)
Subjects: Iodide, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Full Research Paper, Umpolung, lcsh:QD241-441, Nucleophile, lcsh:Organic chemistry, fluorine, Nucleophilic substitution, Reactivity (chemistry), trifluoromethylselenolation, lcsh:Science, selenium, chemistry.chemical_classification, 010405 organic chemistry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, 0104 chemical sciences, Reagent, perfluoroalkylselenolation, Fluorine, lcsh:Q, nucleophilic substitution, Selenium
Abstract: We report herein a practical method to generate CF3Se− (and RFSe−) anions from shelf-stable reagents under iodide activation. Metal-free nucleophilic trifluoromethylselenolations have been then performed with this in situ-generated anion. Perfluoroalkylselenolations have also been described.
Published: 2020

32. Pharmaco-fUS for Characterizing Drugs for Alzheimer’s Disease – The Case of THN201, a Drug Combination of Donepezil Plus Mefloquine

Author: Benjamin Vidal, Marine Droguerre, Marco Valdebenito, Luc Zimmer, Michel Hamon, Franck Mouthon, Mathieu Charvériat, Theranexus [Lyon], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL), Rayet, Béatrice, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: 0301 basic medicine, Drug, connexin, medicine.drug_class, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, media_common.quotation_subject, Disease, Pharmacology, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, mental disorders, pharmaco-fUS, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Donepezil, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, media_common, Cognitive Symptoms, Drug discovery, Mefloquine, business.industry, General Neuroscience, mefloquine, 3. Good health, donepezil, 030104 developmental biology, medicine.anatomical_structure, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Acetylcholinesterase inhibitor, Perspective, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Alzheimer’s disease, 030217 neurology & neurosurgery, medicine.drug, Astrocyte, Neuroscience
Abstract: International audience; Donepezil is a potent acetylcholinesterase inhibitor, largely used worldwide to alleviate cognitive symptoms in Alzheimer’s disease (AD). Beyond the widely described neuronal impact of donepezil, it was recently shown that targeting connexins, the proteins involved in astrocyte network organization, potentiates donepezil efficacy profile using behavioral tests in AD rodent models. We herein present data demonstrating the potential of functional ultrasound imaging to monitor cerebral activity changes after pharmacological challenge in mice. As an example, we showed that although administration of donepezil or mefloquine alone at low dose had only very limited effects on the signal compared to the baseline, their combination produced marked hemodynamic effects in the hippocampus, in line with previously published behavioral data demonstrating a synergic interaction between both drugs. Thus, the present study provides new perspectives, (i) through the use of pharmaco-fUS, a new non-clinical imaging modality, to move forward drug discovery in AD and (ii) by the profiling of two drug treatments on brain dynamics, one used in AD: donepezil, and the other in development: donepezil combined with mefloquine (THN201) as a modulator of astrocyte network.
Published: 2020

33. Pharmacological MRI to investigate the functional selectivity of 5-HT1A receptor biased agonists

Author: Radu Bolbos, Jean-Baptiste Langlois, Jérôme Redouté, Benjamin Vidal, Luc Zimmer, Adrian Newman-Tancredi, Nicolas Costes, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Hospices Civils de Lyon (HCL)
Subjects: 0301 basic medicine, Pharmacology, Agonist, Blood-oxygen-level dependent, Chemistry, medicine.drug_class, [SDV]Life Sciences [q-bio], Somatosensory system, 3. Good health, 03 medical and health sciences, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Retrosplenial cortex, medicine, Functional selectivity, 5-HT1A receptor, Serotonin, Receptor, Neuroscience, 030217 neurology & neurosurgery
Abstract: The emerging concept of "biased agonism" denotes the phenomenon whereby agonists can preferentially direct receptor signalling to specific intracellular responses among the different transduction pathways, thus potentially avoiding side effects and improving therapeutic effects. The aim of this study was to investigate biased agonism by using pharmacological magnetic resonance imaging (phMRI). The cerebral blood oxygen level dependent (BOLD) signal changes induced by increasing doses of two serotonin 5-HT1A receptor biased agonists, NLX-112 and NLX-101, were mapped in anaesthetized rats. Although both compounds display high affinity, selectivity and agonist efficacy for 5-HT1A receptors, NLX-101 is known to preferentially activate post-synaptic receptors, whereas NLX-112 targets both pre- and post-synaptic receptors. We used several doses of agonists in order to determine if the regional selectivity of NLX-101 was dose-dependent. NLX-112 and NLX-101 induced different positive and negative hemodynamic changes patterns at equal doses. Importantly, NLX-101 had no significant effect in regions expressing pre-synaptic receptors contrary to NLX-112. NLX-112 also produced higher BOLD changes than NLX-101 in the orbital cortex, the somatosensory cortex, and the magnocellular preoptic nuclei. In other regions such as the retrosplenial cortex and the dorsal thalamus, the drugs had similar effects. In terms of functional connectivity, NLX-112 induced more widespread changes than NLX-101. The present phMRI study demonstrates that two closely-related agonists display notable differences in their hemodynamic "fingerprints". These data support the concept of biased agonism at 5-HT1A receptors and raise the prospect of identifying novel therapeutics which exhibit improved targeting of brain regions implicated in neuropsychiatric disorders. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.
Published: 2020

34. Functional ultrasound imaging to study brain dynamics: Application of pharmaco-fUS to atomoxetine

Author: Marco Valdebenito, Ludovic Venet, Benjamin Vidal, Mathieu Charvériat, Luc Zimmer, Marine Droguerre, Franck Mouthon, Theranexus [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Hospices Civils de Lyon (HCL)
Subjects: 0301 basic medicine, Male, Pharmaco-fUS, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Brain activity and meditation, Thalamus, Atomoxetine Hydrochloride, Rats, Inbred WKY, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Norepinephrine reuptake inhibitor, medicine, Animals, Ultrasonography, Visual Cortex, Pharmacology, Adrenergic Uptake Inhibitors, business.industry, Dentate gyrus, Atomoxetine, Functional ultrasound imaging, Posterior Thalamic Nuclei, 3. Good health, Rats, 030104 developmental biology, Visual cortex, medicine.anatomical_structure, Mechanism of action, Dentate Gyrus, medicine.symptom, business, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; Highlights• A first evaluation of the potential of fUS during a pharmacological challenge.• ATX modulates cerebral blood volume in areas associated with visual processing.• fUS as a new step to move forwards new drugs to development in neurological disorders.Functional ultrasound (fUS) is a new tool enabling the imaging of brain activity through the regional monitoring of cerebral blood volume (CBV) dynamics. This innovative technique has not yet demonstrated its full potential in pharmacological applications and drug development. In the current proof-of-concept study, the impact of atomoxetine (ATX), a potent norepinephrine reuptake inhibitor and non-stimulant treatment marketed in attention-deficit/hyperactivity-disorder, was evaluated in anesthetized rat using pharmacological functional ultrasound (pharmaco-fUS) at increasing doses (0.3, 1 and 3 mg/kg). Using regions of interest (acute changes of CBV and functional connectivity) or pixel-based (general linear modeling and independent component analysis) analysis, we here demonstrated that ATX consistently displayed a hemodynamic effect in the visual cortex, the dentate gyrus and thalamus, especially visual areas such as lateral posterior thalamic nuclei and lateral geniculate nuclei (LGN). The time profile of ATX effects was dose-dependent, with fastest CBV increases at the highest dose, and longer CBV increases at the intermediate dose. Standardizing the use of pharmaco-fUS could improve our understanding of the mechanism of action of drugs active in the brain and might constitute a new step to move forward in drug development for neurological disorders.
Published: 2020

35. Bayesian Estimation of the ntPET Model in Single-Scan Competition PET Studies

Author: Zacharie Irace, Inés Mérida, Jérôme Redouté, Clara Fonteneau, Marie-Françoise Suaud-Chagny, Jérôme Brunelin, Benjamin Vidal, Luc Zimmer, Anthonin Reilhac, Nicolas Costes, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Université de Lyon, Hospices Civils de Lyon (HCL), Clinical Imaging Research Centre, National University of Singapore (NUS), Rayet, Béatrice, Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: lp-ntPET, Steady state (electronics), Computer science, Physiology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Bayesian inference, brain imaging, lcsh:Physiology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Sampling (signal processing), Robustness (computer science), Physiology (medical), competition model, Sensitivity (control systems), endogenous neurotransmitter release, Original Research, Bayes estimator, lcsh:QP1-981, kinetic modeling, Noise, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, PET, Probability distribution, Algorithm, 030217 neurology & neurosurgery
Abstract: International audience; This paper proposes an innovative method, named b-ntPET, for solving a competition model in PET. The model is built upon the state-of-the-art method called lp-ntPET. It consists in identifying the parameters of the PET kinetic model relative to a reference region that rule the steady state exchanges, together with the identification of four additional parameters defining a displacement curve caused by an endogenous neurotransmitter discharge, or by a competing injected drug targeting the same receptors as the PET tracer. The resolution process of lp-ntPET is however suboptimal due to the use of discretized basis functions, and is very sensitive to noise, limiting its sensitivity and accuracy. Contrary to the original method, our proposed resolution approach first estimates the probability distribution of the unknown parameters using Markov-Chain Monte-Carlo sampling, distributions from which the estimates are then inferred. In addition, and for increased robustness, the noise level is jointly estimated with the parameters of the model. Finally, the resolution is formulated in a Bayesian framework, allowing the introduction of prior knowledge on the parameters to guide the estimation process toward realistic solutions. The performance of our method was first assessed and compared head-to-head with the reference method lp-ntPET using well-controlled realistic simulated data. The results showed that the b-ntPET method is substantially more robust to noise and much more sensitive and accurate than lp-ntPET. We then applied the model to experimental animal data acquired in pharmacological challenge studies and human data with endogenous releases induced by transcranial direct current stimulation. In the drug challenge experiment on cats using [18F]MPPF, a serotoninergic 1A antagonist radioligand, b-ntPET measured a dose response associated with the amount of the challenged injected concurrent 5-HT1A agonist, where lp-ntPET failed. In human [11C]raclopride experiment, contrary to lp-ntPET, b-ntPET successfully detected significant endogenous dopamine releases induced by the stimulation. In conclusion, our results showed that the proposed method b-ntPET has similar performance to lp-ntPET for detecting displacements, but with higher resistance to noise and better robustness to various experimental contexts. These improvements lead to the possibility of detecting and characterizing dynamic drug occupancy from a single PET scan more efficiently.
Published: 2020

36. Constrained tensor decomposition for longitudinal analysis of diffusion imaging data

Author: Claudio Stamile, François Cotton, Sabine Van Huffel, Dominique Sappey-Marinier, RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)
Subjects: Adult, Male, Accuracy and precision, Multiple Sclerosis, Rank (linear algebra), Computer science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 02 engineering and technology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Health Information Management, Image Interpretation, Computer-Assisted, 0202 electrical engineering, electronic engineering, information engineering, Preprocessor, Humans, Tensor, Electrical and Electronic Engineering, ComputingMilieux_MISCELLANEOUS, Complex data type, business.industry, Brain, 020206 networking & telecommunications, Pattern recognition, Middle Aged, Computer Science Applications, Diffusion Tensor Imaging, Bundle, Female, Artificial intelligence, Focus (optics), business, 030217 neurology & neurosurgery, Algorithms, Biotechnology, Diffusion MRI
Abstract: Analysis of complex data is still a challenge in medical image analysis. Due to the heterogeneous information that can be extracted from magnetic resonance imaging (MRI) it can be difficult to fuse such data in a proper way. One interesting case is given by the analysis of diffusion imaging (DI) data. DI techniques give an important variety of information about the status of microstructure in the brain. This is interesting information to use especially in longitudinal setting where the temporal evolution of the pathology is an important added value. In this paper, we propose a new tensor-based framework capable to detect longitudinal changes appearing in DI data in multiple sclerosis (MS) patients. We focus our attention to the analysis of longitudinal changes occurring along different white matter (WM) fiber-bundles. Our main goal is to detect which subset of fibers (within a bundle) and which sections of these fibers contain "pathological" longitudinal changes. The framework consists of three main parts: i) preprocessing of longitudinal diffusion acquisitions and WM fiber-bundles extraction, ii) data tensorization and rank selection, iii) application of a parallelized constrained tensor factorization algorithm to detect longitudinal "pathological" changes. The proposed method was applied on simulated longitudinal variations and on real MS data. High level of accuracy and precision were obtained in the detection of small longitudinal changes along the WM fiber-bundles. ispartof: IEEE Journal of Biomedical and Health Informatics vol:24 issue:4 pages:1137-1148 ispartof: location:United States status: published
Published: 2020

37. Preclinical validation of [18F]2FNQ1P as a specific PET radiotracer of 5-HT6 receptors in rat, pig, non-human primate and human brain tissue

Author: Thibaut Iecker, Benjamin Vidal, Christian Tourvieille, Sandrine Bouvard, Sylvain Fieux, Pierre Courault, Stéphane Emery, Thierry Billard, Luc Zimmer, Sophie Lancelot, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon, Departement de Neurologie (HCL), Hospices Civils de Lyon (HCL), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Synthèse, Utilisation, Réactivité des Composés Organiques et OrganoFluorés (SURCOOF), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences et Techniques Nucléaires (INSTN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Biodistribution, Chemistry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Central nervous system, Antagonist, Caudate nucleus, Human brain, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Pharmacology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine, Molecular Medicine, Radiology, Nuclear Medicine and imaging, Serotonin, Receptor, 5-HT receptor, ComputingMilieux_MISCELLANEOUS
Abstract: Introduction The aim of this study was to perform in-vitro and in-vivo radiopharmacological characterizations of [ 18 F]2FNQ1P, a new PET radiotracer of 5-HT6 receptors, in rat, pig, non-human primate and human tissues. The 5-HT6 receptor is one of the more recently identified serotonin receptors in central nervous system and, because of its role in memory and cognitive processes, is considered as a promising therapeutic target. Methods In-vitro autoradiography and saturation binding assays were performed in postmortem brain tissues from rat, pig, non-human primate and human caudate nucleus, completed by serum stability assessment in all species and cerebral radiometabolite and biodistribution studies in rat. Results In all species, autoradiography data revealed high binding levels of [ 18 F]2FNQ1P in cerebral regions with high 5-HT6 receptor density. Binding was blocked by addition of SB258585 as a specific antagonist. Binding assays provided KD and Bmax values of respectively 1.34 nM and 0.03 pmol·mg−1 in rat, 0.60 nM and 0.04 pmol·mg−1 in pig, 1.38 nM and 0.07 pmol·mg−1 in non-human primate, and 1.39 nM and 0.15 pmol·mg−1 in human caudate nucleus. In rat brain, the proportion of unmetabolized [ 18 F]2FNQ1P was >99% 5 min after iv injection and 89% at 40 min. The biodistribution studies found maximal radioactivity in lungs and kidneys (3.5 ± 1.2% ID/g and 2.0 ± 0.7% ID/g, respectively, 15 min post-injection). Conclusion These radiopharmacological data confirm that [ 18 F]2FNQ1P is a specific radiotracer for molecular imaging of 5-HT6 receptors and suggest that it could be used as a radiopharmaceutical in humans.
Published: 2020

38. Unrelated parallel machines scheduling with setup times in textile industry

Author: Berthier, Alice, Yalaoui, Alice, Chehade, Hicham, Yalaoui, Farouk, Amodeo, Lionel, Bouillot, C., Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

39. Neural correlates of verbal working memory in children with epilepsy with centro-temporal spikes

Author: Julitta de Bellescize, Vania Herbillon, Agathe Laurent, Faustine Ilski, Alexandra Montavont, Jean-Philippe Lachaux, Philippe Ryvlin, Karine Ostrowsky-Coste, Alexis Arzimanoglou, Carolina Ciumas, Mani Saignavongs, Marc Hermier, Danielle Ibarrola, Eleni Panagiotakaki, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Des Épilepsies de l'Enfant et l'adolescent (IDÉE), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], CCSD, Accord Elsevier, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: medicine.medical_specialty, BCECTS, Children with epilepsy, Rolandic epilepsy, Verbal, Working memory, fMRI, [SDV]Life Sciences [q-bio], Cognitive Neuroscience, Audiology, Neuropsychological Tests, lcsh:Computer applications to medicine. Medical informatics, behavioral disciplines and activities, 050105 experimental psychology, Lateralization of brain function, lcsh:RC346-429, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Child, lcsh:Neurology. Diseases of the nervous system, Neural correlates of consciousness, Brain Mapping, medicine.diagnostic_test, business.industry, 05 social sciences, Neuropsychology, Brain, Regular Article, medicine.disease, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Behavioral data, Memory, Short-Term, Neurology, lcsh:R858-859.7, Neurology (clinical), Functional magnetic resonance imaging, business, 030217 neurology & neurosurgery
Abstract: Highlights • We investigated working memory in patients with ECTS and age-matched controls using a verbal working memory task. • Children with ECTS showed altered behavioral and fMRI responses to verbal working with increasing difficulty level. • Children with ECTS demonstrated reduced capacity to sustain high WM load., Background Previous functional magnetic resonance imaging (fMRI) studies have identified brain systems underlying different components of working memory (WM) in healthy subjects. The aim of this study was to compare the functional integrity of these neural networks in children with self-limited childhood epilepsy with centro-temporal spikes (ECTS) as compared to healthy controls, using a verbal working memory task (WMT). Methods Functional MRI of WM in seventeen 6-to-13 year-old children, diagnosed with ECTS, and 17 sex- and age-matched healthy controls were conducted at 3 T. To estimate BOLD responses during the maintenance of low, medium, and high WMT loads, we used a Sternberg verbal WMT. Neuropsychological testing prior to scanning and behavioral data during scanning were also acquired. Results Behavioral performances during WMT, in particular accuracy and response time, were poorer in children with ECTS than in controls. Increased WM load was associated with increased BOLD signal in all subjects, with significant clusters detected in frontal and parietal regions, predominantly in the left hemisphere. However, under the high load condition, patients showed reduced activation in the frontal, temporal and parietal regions as compared to controls. In brain regions where WM-triggered BOLD activation differed between groups, this activation correlated with neuropsychological performances in healthy controls but not in patients with ECTS, further suggesting WM network dysfunction in the latter. Conclusion Children with ECTS differ from healthy controls in how they control WM processes during tasks with increasing difficulty level, notably for high WM load where patients demonstrate both reduced BOLD activation and behavioral performances.
Published: 2020

40. 18F-F13640 PET imaging of functional receptors in humans

Author: Frédéric Dailler, Nicolas Costes, Thierry Billard, Adrian Newman-Tancredi, Matthieu Colom, Luc Zimmer, Jérôme Redouté, Didier Le Bars, Florent Gobert, Radiopharmaceutical and Neurochemical Biomarkers Team (BioRaN), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Department of Anesthesia and Intensive Care Medicine, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Synthèse, Utilisation, Réactivité des Composés Organiques et OrganoFluorés (SURCOOF), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Neurolixis, Hospices Civils de Lyon (HCL), Centre National de la Recherche Scientifique (CNRS)-École Supérieure Chimie Physique Électronique de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École Supérieure Chimie Physique Électronique de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Agonist, Postmortem studies, medicine.diagnostic_test, Chemistry, medicine.drug_class, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Standardized uptake value, General Medicine, Human brain, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Pharmacology, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Neuroimaging, Positron emission tomography, In vivo, 030220 oncology & carcinogenesis, medicine, Radiology, Nuclear Medicine and imaging, Receptor, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; The vast majority of PET radiopharmaceuticals used for receptor neuroimaging are antagonists. This is particularly true for 5-HT1A receptor radiopharmaceuticals such as 18F-MPPF or 11C-WAY100635. These radiolabeled antagonists allow PET neuroimaging of the total pool of receptors, regardless of their functional state. In contrast, agonists bind preferentially to the functionally active state of receptors, a pharmacological property that has not yet been exploited for PET imaging of functional 5-HT1A receptors [1]. To this end, we have developed a highly selective 5-HT1A receptor agonist, 18FF13640, and validated it in animal models [2]. A postmortem study in Alzheimer subjects showed that the in vitro binding of 18F-F13640 differs from that of 18F-MPPF, the prototypical radiopharmaceutical [3]. Here we show the first human brain image obtained in vivo with 18F-F13640 (study registration, EudraCT2017-002722-21). A summed brain PET image was obtained in a 32-year-old healthy man after IV injection of the radiopharmaceutical (90-min scan). 18F-F13640 brain distribution, expressed by the standardized uptake value with the body weight (SUV bw), showed a binding pattern different from that seen with conventional antagonist 5-HT1A radiopharmaceuticals. Although the binding regions are well correlated to the density of 5-HT1A receptors, the ROIs are mainly cortical, indicating that these brain regions are enriched in functionally active receptors. 18F-F13640 is the first radiopharmaceutical that enables in vivo investigation of functional 5-HT1A receptors that are likely to be altered in pathological conditions such as neurodegenerative diseases or psychiatric disorders. The development of this agonist PET radiopharmaceutical opens new opportunities for nuclear medicine.
Published: 2020

41. Visible‐Light‐Mediated Metal‐Free Synthesis of Trifluoromethylselenolated Arenes

Author: Lhoussain Khrouz, Vincent Debrauwer, Thierry Billard, Maurice Médebielle, Clément Ghiazza, Cyrille Monnereau, Anis Tlili, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Synthèse, Utilisation, Réactivité des Composés Organiques et OrganoFluorés (SURCOOF), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie - UMR5182 (LC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), Synthèse de Molécules d'Intérêt Thérapeutique (SMITh), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: Reaction mechanism, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, law.invention, chemistry.chemical_compound, law, [CHIM]Chemical Sciences, Electron paramagnetic resonance, ComputingMilieux_MISCELLANEOUS, Trifluoromethyl, [CHIM.ORGA]Chemical Sciences/Organic chemistry, 010405 organic chemistry, Chemistry, General Medicine, [CHIM.CATA]Chemical Sciences/Catalysis, [CHIM.MATE]Chemical Sciences/Material chemistry, General Chemistry, 0104 chemical sciences, Reagent, Photocatalysis, Cyclic voltammetry, Luminescence, Visible spectrum
Abstract: The first visible-light-mediated synthesis of trifluoromethylselenolated arenes under metal-free conditions is reported. The use of an organic photocatalyst enables the trifluoromethylselenolation of arene diazonium salts using the shelf-stable reagent trifluoromethyl tolueneselenosulfonate at room temperature. The reaction does not require the presence of any additives and shows high functional-group tolerance, covering a very broad range of starting materials. Mechanistic investigations, including EPR spectroscopy, luminescence investigations, and cyclic voltammetry allow rationalization of the reaction mechanism.
Published: 2018

42. Sécurisation de la prise en charge médicamenteuse des patients sous antipsychotiques : impact de la collaboration médico-pharmaceutique à la Maison d’Arrêt de Lyon-Corbas

Author: C. Abel-coindoz, G. Giret, D. Cabelguenne, Luc Zimmer, A. Mauchauffée, C. Bertin, L. Lalande, C. Picard, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Arts and Humanities (miscellaneous), [SDV]Life Sciences [q-bio], 3. Good health, 030227 psychiatry
Abstract: Resume Objectif L’iatrogenie des antipsychotiques, en plus des facteurs lies au mode de vie, est en partie responsable de la surmortalite des patients traites. Un suivi clinique et paraclinique des patients est recommande et necessaire. Dans ce contexte un projet collaboratif a ete mene au sein de l’unite sanitaire sur l’optimisation du suivi des patients sous antipsychotiques dans le contexte du milieu penitentiaire. Sont associes dans ce projet medecins generalistes, psychiatres et pharmaciens. L’objectif de l’etude est d’evaluer l’evolution de la qualite du suivi des patients traites par antipsychotiques. Methode Il s’agit d’une etude retrospective incluant tous les patients suivis et traites par antipsychotiques pendant au moins 6 mois durant les annees 2011 et 2015. Le recueil de donnees a ete realise a partir des dossiers medicaux. L’indicateur choisi pour apprecier la qualite du suivi etait le pourcentage de conformite des parametres paracliniques pour chacun des patients au regard du referentiel predefini en concertation medico-pharmaceutique. Resultats En 2015 versus 2011, la qualite de suivi s’est amelioree pour 9 des 10 parametres etudies, avec une amelioration statistiquement significative pour 7 d’entre eux : Indice de Masse Corporelle, bilan lipidique, numeration formule sanguine, bilan hepatique, ionogramme, glycemie et fonction renale. Conclusion Cette etude a permis de demontrer que les axes d’amelioration definis en concertation medico-pharmaceutique ont eu un impact effectif sur la qualite de suivi des patients sous antipsychotiques.
Published: 2019

43. In vivo biased agonism at 5-HT1A receptors: characterisation by simultaneous PET/MR imaging

Author: Jérôme Redouté, Sylvain Fieux, Nicolas Costes, Marjorie Villien, Frédéric Bonnefoi, Didier Le Bars, Adrian Newman-Tancredi, Luc Zimmer, Benjamin Vidal, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Neurolixis, and Hospices Civils de Lyon (HCL)
Subjects: Male, 0301 basic medicine, Cingulate cortex, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV]Life Sciences [q-bio], Context (language use), Multimodal Imaging, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Neuroimaging, Functional selectivity, medicine, Animals, 5-HT receptor, Neuropharmacology, Pharmacology, medicine.diagnostic_test, Brain, Serotonin 5-HT1 Receptor Agonists, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, nervous system, chemistry, Positron-Emission Tomography, Receptor, Serotonin, 5-HT1A, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cats, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MPPF, Functional magnetic resonance imaging, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; In neuropharmacology, the recent concept of 'biased agonism' denotes the capacity of certain agonists to target-specific intracellular pathways of a given receptor in specific brain areas. In the context of serotonin pharmacotherapy, 5-HT1A receptor-biased agonists could be of great interest in several neuropsychiatric disorders. The aim of this study was to determine whether biased agonists could be differentiated in terms of regional targeting by use of simultaneous functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) brain imaging. We compared two 5-HT1A-biased agonists, NLX-112 and NLX-101, injected at three different doses in anaesthetised cats (n = 4). PET imaging was acquired for 90 min after bolus administration followed by constant infusion of the 5-HT1A radiotracer, [18F]MPPF. Drug occupancy was evaluated after injection at 50 min and BOLD fMRI was simultaneously acquired to evaluate subsequent brain activation patterns. 5-HT1A receptor occupancy was found to be dose-dependent for both agonists, but differed in magnitude and spatial distribution at equal doses with distinct BOLD patterns. Functional connectivity, as measured by BOLD signal temporal correlations between regions, was also differently modified by NLX-112 or NLX-101. Voxel-based correlation analyses between PET and fMRI suggested that NLX-112 stimulates both 5-HT1A autoreceptors and post-synaptic receptors, whereas NLX-101 preferentially stimulates post-synaptic cortical receptors. In cingulate cortex, the agonists induced opposite BOLD signal changes in response to receptor occupancy. These data constitute the first simultaneous exploration of 5-HT1A occupancy and its consequences in terms of brain activation, and demonstrates differential signalling by two 5-HT1A-biased agonists. Combined PET/fMRI represents a powerful tool in neuropharmacology, and opens new ways to address the concept of biased agonism by translational approaches.
Published: 2018

44. Fe-mediated nucleophilic trifluoromethylselenolation of activated alkyl bromides via umpolung reactivity of trifluoromethyl tolueneselenosulfinate

Author: Guillaume Dagousset, Emmanuel Chefdeville, Bruce Pégot, Thierry Billard, Arnaud De Zordo-Banliat, Emmanuel Magnier, Kevin Grollier, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and ANR-18-CE07-0039,SAFA,Selenium et Fluor Associés: le mariage de 2 stars(2018)
Subjects: Iron, 010402 general chemistry, 01 natural sciences, Biochemistry, Medicinal chemistry, Iron powder, Umpolung, Selenium, chemistry.chemical_compound, Nucleophile, Drug Discovery, [CHIM]Chemical Sciences, Reactivity (chemistry), Trifluoromethylselenolation, Alkyl, chemistry.chemical_classification, Trifluoromethyl, 010405 organic chemistry, fungi, Organic Chemistry, food and beverages, Fluorine, 0104 chemical sciences, chemistry, Reagent, SN2 reaction
Abstract: International audience; Trifluoromethyl tolueneselenosulfonate is a versatile reagent which can be reduced by iron powder to generate in situ trifluoromethylselenolate anion. This species can then react with alkyl bromide to perform SN2 reaction.
Published: 2021

45. Oxytocin Fails to Recruit Serotonergic Neurotransmission in the Autistic Brain

Author: Nicolas Costes, Raphaelle Mottolese, Angela Sirigu, Didier Le Bars, Marie-Maude Geoffray, Arthur Lefevre, Jérôme Redouté, Marion Leboyer, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre d'économie de la Sorbonne (CES), Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Centre Hospitalier le Vinatier [Bron], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut de biologie et chimie des protéines [Lyon] (IBCP)
Subjects: Adult, Male, 0301 basic medicine, Serotonin, medicine.medical_specialty, Autism Spectrum Disorder, Cognitive Neuroscience, Neuropeptide, Oxytocin, Serotonergic, Placebo, Synaptic Transmission, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Administration, Intranasal, [CHIM.ORGA]Chemical Sciences/Organic chemistry, business.industry, Brain, Human brain, medicine.disease, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, chemistry, Positron-Emission Tomography, Receptor, Serotonin, 5-HT1A, Autism, MPPF, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Oxytocin (OT), a neuropeptide involved in affiliation has been shown to enhance social skills in patients with autism spectrum disorders (ASD). Nevertheless, OT improvements seem ephemeral. Animal research has demonstrated OT action on serotonin (5-HT), an interaction that we also found in the healthy human brain. Whether such synaptic interplay also occurs in ASD patients is unknown. To address this issue, we mapped the effects of intranasal OT on 5-HT in 18 patients with ASD and 24 healthy controls (HC) in a double blind, placebo controlled, within subject PET-scan experiment. Each participant underwent two scans: baseline and spray (OT or placebo). Using the radiotracer [18 F]MPPF, marking the 5-HT 1A receptor (5-HT1AR), we measured MPPF-Binding Potential (BP) as an index of OT-induced serotonin functional modulation. At baseline ASD patients did not differ from controls for 5-HT1AR concentration and distribution. However, while OT significantly increased MPPF BP in several brain regions of HC, no changes were observed in the ASD group. Serotonin serum concentration analysis corroborated these results. Our findings suggest a disturbed OT-serotonin interaction in autism. This may limit the potential benefits of OT in these patients and open the ways to investigate combined OT-serotonin treatments.
Published: 2017

46. Verbal and musical short-term memory: Variety of auditory disorders after stroke

Author: Yohana Lévêque, Patrick Bouchet, Sébastien Daligault, Barbara Tillmann, Lesly Fornoni, Anne Caclin, Julien Jung, Norbert Nighoghossian, Salem Hannoun, Catherine Hirel, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon, Departement de Neurologie (HCL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Melody, Cognitive Neuroscience, Short-term memory, Experimental and Cognitive Psychology, Neuropsychological Tests, Amusia, computer.software_genre, behavioral disciplines and activities, 050105 experimental psychology, Brain Ischemia, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), Voxel, Aphasia, Developmental and Educational Psychology, medicine, Humans, 0501 psychology and cognitive sciences, Neuropsychological assessment, Stroke, Aged, Aged, 80 and over, medicine.diagnostic_test, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Cognition, Middle Aged, medicine.disease, Memory, Short-Term, Neuropsychology and Physiological Psychology, Female, medicine.symptom, Psychology, computer, Music, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: International audience; Auditory cognitive deficits after stroke may concern language and/or music processing, resulting in aphasia and/or amusia. The aim of the present study was to assess the potential deficits of auditory short-term memory for verbal and musical material after stroke and their underlying cerebral correlates with a Voxel-based Lesion Symptom Mapping approach (VLSM). Patients with an ischemic stroke in the right (N=10) or left (N=10) middle cerebral artery territory and matched control participants (N=14) were tested with a detailed neuropsychological assessment including global cognitive functions, music perception and language tasks. All participants then performed verbal and musical auditory short-term memory (STM) tasks that were implemented in the same way for both materials. Participants had to indicate whether series of four words or four tones presented in pairs, were the same or different. To detect domain-general STM deficits, they also had to perform a visual STM task. Behavioral results showed that patients had lower performance for the STM tasks in comparison with control participants, regardless of the material (words, tones, visual) and the lesion side. The individual patient data showed a double dissociation between some patients exhibiting verbal deficits without musical deficits or the reverse. Exploratory VLSM analyses suggested that dorsal pathways are involved in verbal (phonetic), musical (melodic), and visual STM, while the ventral auditory pathway is involved in musical STM.
Published: 2017

47. 11 C-Labeling: Intracyclic Incorporation of Carbon-11 into Heterocycles

Author: Liger, François, Cadarossanesaib, Florence, Iecker, Thibaut, Tourvieille, Christian, Le Bars, Didier, Billard, Thierry, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon, Synthèse, Utilisation, Réactivité des Composés Organiques et OrganoFluorés (SURCOOF), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: [CHIM]Chemical Sciences, [CHIM.RADIO]Chemical Sciences/Radiochemistry, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Labeling of heterocycles with carbon-11 is generally performed through peripheral functionalizations and more scarcely inside heterocyclic core. Such less common approach usually requires preliminary multi-step synthesis of reactive species. Herein, a cyclization reaction by direct use of cyclotron-produced [ 11 C]CO2 is described to obtain various heterocycles intracyclically labeled in only 10 minutes.
Published: 2019

48. Comparison of perfusion MRI parameters to best identify PET penumbra and final infarct: a PET/MRI simultaneous study in a stroke model

Author: Debatisse, Justine, Eker, Omer, Wateau, Océane, Costes, Nicolas, Lukaszewicz, Anne-Claire, Le Bars, Didier, Troalen, Thomas, Contamin, Hugues, Cho, Tae-Hee, Canet Soulas, Emmanuelle, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Siemens Healthineers [Saint-Denis], Université Jean Monnet [Saint-Étienne] (UJM), Hospices Civils de Lyon (HCL), CYNBIOSE, Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Lyon, French National Research Agency (ANR) [ ANR-15-CE17-0020], French National Research Agency (ANR) [ANR-16-RHUS-0009], International Society of Cerebral Blood Flow and Metabolism (ISCBFM). Bethesda, USA., and ProdInra, Migration
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

49. Impaired vocal communication, sleep-related discharges and transient alterations of slow-wave sleep and of brainmicrostructure in developing mice lacking the epilepsy and language related GluN2A subunit of NMDA receptors

Author: Salmi, Manal, Del Gallo, Federico, Minlebaev, Marat, Bolbos, Radu, Zakharov, Andrei, Pauly, Vanessa, Perron, Pauline, Bauer, Sylvian, Pons-Bennaceur, Alexandre, Corby-Pellegrino, Séverine, Aniksztejn, Laurent, Lenck-Santini, Pierre-Pascal, Epsztein, Jérôme, Khazipov, Roustem, Burnashev, Nail, Bertini, Giuseppe, Szepetowski, Pierre, Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), University of Verona (UNIVR), Kazan Federal University (KFU), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Verona = University of Verona (UNIVR), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [SDV]Life Sciences [q-bio], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

50. MAPSSIC, a Novel CMOS Intracerebral Positrons Probe for Deep Brain Imaging in Awake and Freely Moving Rats: A Monte Carlo Study

Author: Ammour, L., Heymes, J., Bautista, M., Fieux, S., Gensolen, F., Kachel, M., Dubois, André, Lefebvre, Fabrice, Pain, F., Pangaud, P., Pinot, L., Baudot, J., Gisquet-Verrier, Pascale, Lanièce, Philippe, Morel, C., Zimmer, L., Verdier, M., Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Département Recherches Subatomiques (DRS-IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), laniece, philippe, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)
Subjects: [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract: International audience; Preclinical behavior neuroimaging gathers simultaneous assessment of behavior and functional brain imaging. It is a potential key breakthrough to improve the understanding of brain processes and assess the validity of preclinical studies in drug development. Achieving such a combination is difficult, anesthesia or restraints inherent to conventional nuclear imaging preclude its use for behavior studies. In that context, we have proposed an original strategy using submillimetric probes to directly measures positrons inside the rat brain. This paper gives the results of Monte Carlo simulations of a new generation of intracerebral positron probe based on a CMOS Monolithic Active Pixel Sensor. We present the results obtained for a probe into a large homogeneous volume of radioactive water (18 F) leading to a sensitivity of 0.88 cps · Bq −1 · mm 3 and a mean energy deposition by positrons of 15.1 keV. Simulation in simplified brain-shaped sources modeling a 11 C-raclopride experiment shows that the implanted volume modeling the left putamen contribute to 92.4 % of the signal from positrons. We also investigate the effects of the thickness of the sensitive layer, the energy threshold and pixel dimensions on the detection capacities of the sensor. We demonstrate that an increase in the sensitive thickness from 18 to 190 µm would lead to an increase of positrons sensitivity by a factor of 1.74, but to a decrease of the direct (positrons) to indirect (γ-rays and electrons) sensitivity ratio by a factor of 1.59. Finally we show that for a threshold lower than about 5 keV the effect of the pixel dimensions is negligible.
Published: 2019

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