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1. Repeated exposure to nanosecond high power pulsed microwaves increases cancer incidence in rat.

Author

René de Seze, Carole Poutriquet, Christelle Gamez, Emmanuelle Maillot-Maréchal, Franck Robidel, Anthony Lecomte, and Caroline Fonta

Subjects
Medicine, Science
Abstract

High-power microwaves are used to inhibit electronics of threatening military or civilian vehicles. This work aims to assess health hazards of high-power microwaves and helps to define hazard threshold levels of modulated radiofrequency exposures such as those emitted by the first generations of mobile phones. Rats were exposed to the highest possible field levels, under single acute or repetitive exposures for eight weeks. Intense microwave electric fields at 1 MV m-1 of nanoseconds duration were applied from two sources at different carrier frequencies of 10 and 3.7 GHz. The repetition rate was 100 pps, and the duration of train pulses lasted from 10 s to twice 8 min. The effects on the central nervous system were evaluated, by labelling brain inflammation marker GFAP and by performing different behavioural tests: rotarod, T-maze, beam-walking, open-field, and avoidance test. Long-time survival was measured in animals repeatedly exposed, and anatomopathological analysis was performed on animals sacrificed at two years of life or earlier in case of precocious death. Control groups were sham exposed. Few effects were observed on behaviour. With acute exposure, an avoidance reflex was shown at very high thermal level (22 W kg-1); GFAP was increased some days after exposure. Most importantly, with repeated exposures, survival time was 4-months shorter in the exposed group, with eleven animals exhibiting a large sub-cutaneous tumour, compared to two in the sham group. A residual X-ray exposure was also present in the beam (0.8 Gy), which is probably not a bias for the observed result. High power microwaves below thermal level in average, can increase cancer prevalence and decrease survival time in rats, without clear effects on behaviour. The parameters of this effect need to be further explored, and a more precise dosimetry to be performed.

Published
2020
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2. Prominent facilitation at beta and gamma frequency range revealed with physiological calcium concentration in adult mouse piriform cortex in vitro.

Author

Marie Gleizes, Simon P Perrier, Caroline Fonta, and Lionel G Nowak

Subjects
Medicine, Science
Abstract

Neuronal activity is characterized by a diversity of oscillatory phenomena that are associated with multiple behavioral and cognitive processes, yet the functional consequences of these oscillations are not fully understood. Our aim was to determine whether and how these different oscillatory activities affect short-term synaptic plasticity (STP), using the olfactory system as a model. In response to odorant stimuli, the olfactory bulb displays a slow breathing rhythm as well as beta and gamma oscillations. Since the firing of olfactory bulb projecting neurons is phase-locked with beta and gamma oscillations, structures downstream from the olfactory bulb should be driven preferentially at these frequencies. We examined STP exhibited by olfactory bulb inputs in slices of adult mouse piriform cortex maintained in vitro in an in vivo-like ACSF (calcium concentration: 1.1 mM). We replaced the presynaptic neuronal firing rate by repeated electrical stimulation (frequency between 3.125 and 100 Hz) applied to the lateral olfactory tract. Our results revealed a considerable enhancement of postsynaptic response amplitude for stimulation frequencies in the beta and gamma range. A phenomenological model of STP fitted to the data suggests that the experimental results can be explained by the interplay between three mechanisms: a short-term facilitation mechanism (time constant ≈160 msec), and two short-term depression mechanisms (recovery time constants

Published
2017
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3. Multiple Functions of MSCA-1/TNAP in Adult Mesenchymal Progenitor/Stromal Cells

Author

David Estève, Jean Galitzky, Anne Bouloumié, Caroline Fonta, René Buchet, and David Magne

Subjects
Internal medicine, RC31-1245
Abstract

Our knowledge about mesenchymal stem cells has considerably grown in the last years. Since the proof of concept of the existence of such cells in the 70s by Friedenstein et al., a growing mass of reports were conducted for a better definition of these cells and for the reevaluation from the term “mesenchymal stem cells” to the term “mesenchymal stromal cells (MSCs).” Being more than a semantic shift, concepts behind this new terminology reveal the complexity and the heterogeneity of the cells grouped in MSC family especially as these cells are present in nearly all adult tissues. Recently, mesenchymal stromal cell antigen-1 (MSCA-1)/tissue nonspecific alkaline phosphatase (TNAP) was described as a new cell surface marker of MSCs from different tissues. The alkaline phosphatase activity of this protein could be involved in wide range of MSC features described below from cell differentiation to immunomodulatory properties, as well as occurrence of pathologies. The present review aims to decipher and summarize the role of TNAP in progenitor cells from different tissues focusing preferentially on brain, bone marrow, and adipose tissue.

Published
2016
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6. Inhibitors of ectonucleotidases have paradoxical effects on synaptic transmission in the mouse cortex

Author

Marie Gleizes, Caroline Fonta, Lionel G. Nowak, 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, and Fonta, Caroline

Subjects
ALPL, Adenosine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Synaptic Transmission, Biochemistry, Mice, Cellular and Molecular Neuroscience, Adenosine Triphosphate, Nucleotidases, Animals, ARL 67156, MLS-0038949, Enzyme Inhibitors, MSCA-1, 5'-Nucleotidase, Evoked Potentials, Cerebral Cortex, CD39, Receptor, Adenosine A1, MLS- 0038949, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alkaline Phosphatase, Olfactory Bulb, Adenosine Monophosphate, Electric Stimulation, Adenosine A1 Receptor Agonists, Mice, Inbred C57BL, CD73, Female
Abstract

International audience; Extracellular adenosine plays prominent roles in the brain in both physiological and pathological conditions. Adenosine can be generated following the degradation of extracellular nucleotides by various types of ectonucleotidases. Several ectonucleotidases are present in the brain parenchyma: ecto-nucleotide triphosphate diphosphohydrolases 1 and 3 (NTPDase 1 and 3), ecto-nucleotide pyrophosphatase/ phosphodiesterase 1 (NPP 1), ecto-5’-nucleotidase (eN), and tissue non-specific alkaline phosphatase (TNAP, whose function in the brain has received little attention). Here we examined, in a living brain preparation, the role of these ectonucleotidases in generating extracellular adenosine. We recorded local field potentials evoked by electrical stimulation of the lateral olfactory tract in the mouse piriform cortex in vitro. Variations in adenosine level were evaluated by measuring changes in presynaptic inhibition generated by adenosine A1 receptors (A1Rs) activation. A1R-mediated presynaptic inhibition was present endogenously and was enhanced by bath-applied AMP and ATP. We hypothesized that inhibiting ectonucleotidases would reduce extracellular adenosine concentration, which would result in a weakening of presynaptic inhibition. However, inhibiting TNAP had no effect in controlling endogenous adenosine action and no effect on presynaptic inhibition induced by bath-applied AMP. Furthermore, contrary to our expectation, inhibiting TNAP reinforced, rather than reduced, presynaptic inhibition induced by bath-applied ATP. Similarly, inhibition of NTPDase 1 and 3, NPP1, and eN induced stronger, rather than weaker presynaptic inhibition, both in endogenous condition and with bath-applied ATP and AMP. Consequently, attempts to suppress the functions of extracellular adenosine by blocking its extracellular synthesis in living brain tissue could have functional impacts opposite to those anticipated.

Published
2022

10. Sulci 3D mapping from human cranial endocasts: A powerful tool to study hominin brain evolution

Author

Edwin John de Jager, Laurent Risser, Muriel Mescam, Caroline Fonta, Amélie Beaudet, Institut de Mathématiques de Toulouse UMR5219 (IMT), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-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)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), 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), and Université de Toulouse (UT)

Subjects
Radiological and Ultrasound Technology, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Skull, Brain, Hominidae, micro-CT, Biological Evolution, South Africa, Neurology, sulcal pattern, density map, virtual endocasts, Animals, Humans, Radiology, Nuclear Medicine and imaging, atlas, Neurology (clinical), Anatomy, human cortex
Abstract

International audience; Key questions in paleoneurology concern the timing and emergence of derived cerebral features within the human lineage. Endocasts are replicas of the internal table of the bony braincase that are widely used in paleoneurology as a proxy for reconstructing a timeline for hominin brain evolution in the fossil record. The accurate identification of cerebral sulci imprints in endocasts is critical for assessing the topographic extension and structural organisation of cortical regions in fossil hominins. High-resolution imaging techniques combined with established methods based on population-specific brain atlases offer new opportunities for tracking detailed endocranial characteristics. This study provides the first documentation of sulcal pattern imprints from the superolateral surface of the cerebrum using a population-based atlas technique on extant human endocasts. Human crania from the Pretoria Bone Collection (South Africa) were scanned using micro-CT. Endocasts were virtually extracted, and sulci were automatically detected and manually labelled. A density map method was applied to project all the labels onto an averaged endocast to visualise the mean distribution of each identified sulcal imprint. This method allowed for the visualisation of inter-individual variation of sulcal imprints, for example, frontal lobe sulci, correlating with previous brain-MRI studies and for the first time the extensive overlapping of imprints in historically debated areas of the endocast (e.g. occipital lobe). In providing an innovative, non-invasive, observerindependent method to investigate human endocranial structural organisation, our analytical protocol introduces a promising perspective for future research in paleoneurology and for discussing critical hypotheses on the evolution of cognitive abilities among hominins.

Published
2022

12. 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

13. In vivo localization of cortical areas using a 3D computerized atlas of the marmoset brain

Author

Sandra Lebreton, Nathalie Vayssiere, Pascal Girard, Marcello G. P. Rosa, Laurent Risser, Caroline Fonta, Samuel Boucher, Amirouche Sadoun, Muriel Mescam, Kuzma Strelnikov, Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Monash University [Clayton], Centre of Excellence for Integrative Brain Function, Monash University, Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-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)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), and Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Cerebellum, Histology, Computer science, [SDV]Life Sciences [q-bio], Neuroimaging, 050105 experimental psychology, White matter, [SCCO]Cognitive science, 03 medical and health sciences, Imaging, Three-Dimensional, 0302 clinical medicine, biology.animal, Image Processing, Computer-Assisted, medicine, Animals, 0501 psychology and cognitive sciences, Segmentation, ComputingMilieux_MISCELLANEOUS, biology, General Neuroscience, 05 social sciences, Brain atlas, Brain, Marmoset, Haplorhini, biology.organism_classification, Magnetic Resonance Imaging, Callithrix, Olfactory bulb, medicine.anatomical_structure, Female, Anatomy, Neuroscience, Software, 030217 neurology & neurosurgery, Tractography
Abstract

We created a volumetric template of the marmoset (Callithrix jacchus) brain, which enables localization of the cortical areas defined in the Paxinos et al. (The marmoset brain in stereotaxic coordinates. Elsevier Academic Press, Cambridge, 2012) marmoset brain atlas, as well as seven broader cortical regions (occipital, temporal, parietal, prefrontal, motor, limbic, insular), different brain compartments (white matter, gray matter, cerebro-spinal fluid including ventricular spaces), and various other structures (brain stem, cerebellum, olfactory bulb, hippocampus). The template was designed from T1-weighted MR images acquired using a 3 T MRI scanner. It was based on a single fully segmented marmoset brain image, which was transported onto the mean of 13 adult marmoset brain images using a diffeomorphic strategy that fully preserves the brain topology. In addition, we offer an automatic segmentation pipeline which fully exploits the proposed template. The segmentation pipeline was quantitatively assessed by comparing the results of manual and automated segmentations. An associated program, written in Python, can be used from a command-line interface, or used interactively as a module of the 3DSlicer software. This program can be applied to the analysis of multimodal images, to map specific cortical areas in lesions or to define the seeds for further tractography analyses.

Published
2019

14. Key periods of cognitive decline in a nonhuman primate model of cognitive aging, the common marmoset (Callithrix jacchus)

Author

Caroline Fonta, Pascal Girard, Amirouche Sadoun, Maxime Rosito, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Images et Modèles, 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), and Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Aging, Spatial memory, Executive Function, 03 medical and health sciences, 0302 clinical medicine, biology.animal, Animals, Learning, Cognitive Dysfunction, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Spatial Memory, Behavior, Animal, biology, Working memory, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, Marmoset, Callithrix, Cognition, Executive functions, biology.organism_classification, Disease Models, Animal, 030104 developmental biology, Cognitive Aging, Life expectancy, Female, Neurology (clinical), Geriatrics and Gerontology, Psychology, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract

It is well established that human life expectancy increases considerably with an ever-growing number of people suffering from age-related cognitive decline and degenerative brain diseases. This necessitates the development of animal models to counteract or stop the progression of the decline early enough. Presently, primate models are few, and many studies argue for the marmoset as an interesting primate model presenting a short life span and being easily available in research laboratories. In this article, we propose the marmoset as a valid model for cognitive decline. Using a computer touch screen, we trained 35 marmosets from 2 to 14 years of age to perform reversal learning and delayed-matching-to-position tasks. We found typical age-related cognitive deficits related to executive functions and spatial working memory. Applying a recursive algorithm, we detected 2 critical periods from which deficits appear. Mainly, response strategy deficits appear from age 4, whereas impairments in inhibitory control appear from age 7–8. Furthermore, the presence of outliers, sometimes at an early age, suggests pathological cognitive deficits that would require imaging exploration in parallel to behavior.

Published
2019

15. Tissue-nonspecific alkaline phosphatase is an anti-inflammatory nucleotidase

Author

E.L. Matera, J. Como, René Buchet, C. Mansouri, Caroline Fonta, Saida Mebarek, Anne Briolay, Marie Gleizes, A. El Jamal, José Luis Millán, Laurence Bessueille, Etienne Mornet, Charles Dumontet, David Magne, 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), Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), 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), Sanford Burnham Prebys Medical Discovery Institute, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, medicine.medical_specialty, Histology, Physiology, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Anti-Inflammatory Agents, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Calcification, Physiologic, ATP hydrolysis, Nucleotidases, Nucleotidase, Internal medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Osteoblasts, Chemistry, Mesenchymal stem cell, Hypophosphatasia, ALPL, medicine.disease, Alkaline Phosphatase, Adenosine, 030104 developmental biology, Endocrinology, Cytokine, Alkaline phosphatase, medicine.drug
Abstract

International audience; Tissue-nonspecific alkaline phosphatase (TNAP) is necessary for skeletal mineralization by its ability to hydrolyze the mineralization inhibitor inorganic pyrophosphate (PPi), which is mainly generated from extracellular ATP by ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Since children with TNAP deficiency develop bone metaphyseal auto-inflammations in addition to rickets, we hypothesized that TNAP also exerts anti-inflammatory effects relying on the hydrolysis of pro-inflammatory adenosine nucleotides into the anti-inflammatory adenosine. We explored this hypothesis in bone metaphyses of 7-day-old Alpl+/− mice (encoding TNAP), in mineralizing hypertrophic chondrocytes and osteoblasts, and non-mineralizing mesenchymal stem cells (MSCs) and neutrophils, which express TNAP and are present, or can be recruited in the metaphysis. Bone metaphyses of 7-day-old Alpl+/− mice had significantly increased levels of Il-1β and Il-6 and decreased levels of the anti-inflammatory Il-10 cytokine as compared with Alpl+/+ mice. In bone metaphyses, murine hypertrophic chondrocytes and osteoblasts, Alpl mRNA levels were much higher than those of the adenosine nucleotidases Npp1, Cd39 and Cd73. In hypertrophic chondrocytes, inhibition of TNAP with 25 μM of MLS-0038949 decreased the hydrolysis of AMP and ATP. However, TNAP inhibition did not significantly modulate ATP- and adenosine-associated effects in these cells. We observed that part of TNAP proteins in hypertrophic chondrocytes was sent from the cell membrane to matrix vesicles, which may explain why TNAP participated in the hydrolysis of ATP but did not significantly modulate its autocrine pro-inflammatory effects. In MSCs, TNAP did not participate in ATP hydrolysis nor in secretion of inflammatory mediators. In contrast, in neutrophils, TNAP inhibition with MLS-0038949 significantly exacerbated ATP-associated activation and secretion of IL-1β, and extended cell survival. Collectively, these results demonstrate that TNAP is a nucleotidase in both hypertrophic chondrocytes and neutrophils, and that this nucleotidase function is associated with autocrine effects on inflammation only in neutrophils.

Published
2020

16. Repeated exposure to nanosecond high power pulsed microwaves increases cancer incidence in rat

Author

Anthony Lecomte, Caroline Fonta, René de Seze, Christelle Gamez, Emmanuelle Maillot-Marechal, Franck Robidel, Carole Poutriquet, Institut National de l'Environnement Industriel et des Risques (INERIS), Centre de recherche cerveau et cognition (CERCO), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fonta, Caroline, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Time Factors, Carcinogenesis, Social Sciences, Pathology and Laboratory Medicine, Nervous System, 030218 nuclear medicine & medical imaging, Sham group, Rats, Sprague-Dawley, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Psychology, Animal Anatomy, Microwaves, Immune Response, Neurological Tumors, ComputingMilieux_MISCELLANEOUS, Mammals, Multidisciplinary, Behavior, Animal, Physics, Electromagnetic Radiation, Incidence, Eukaryota, Animal Models, [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, Experimental Organism Systems, Oncology, Neurology, 030220 oncology & carcinogenesis, Anesthesia, Pituitary Gland, Physical Sciences, Vertebrates, Anatomy, Research Article, Science, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endocrine System, Research and Analysis Methods, Rodents, Pituitary Tumors, 03 medical and health sciences, Model Organisms, Signs and Symptoms, [SDV.CAN] Life Sciences [q-bio]/Cancer, Diagnostic Medicine, Avoidance Learning, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Microwave Radiation, Animals, Radiometry, Cancer prevalence, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Inflammation, Behavior, business.industry, [SPI.ELEC] Engineering Sciences [physics]/Electromagnetism, Organisms, Biology and Life Sciences, Cancers and Neoplasms, Kidneys, Renal System, Neoplasms, Experimental, Nanosecond, Survival Analysis, Rats, Neuroanatomy, Cancer incidence, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Acute exposure, Amniotes, Reflex, Animal Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Zoology, 030217 neurology & neurosurgery, Microwave, Cell Phone, Neuroscience
Abstract

High-power microwaves are used to inhibit electronics of threatening military or civilian vehicles. This work aims to assess health hazards of high-power microwaves and helps define hazard threshold levels of modulated radiofrequency exposures such as those emitted by the first generations of mobile phones.Rats were exposed to the highest possible field levels, under single acute or repetitive exposures for eight weeks. Intense microwave electric fields at 1 MV/m of nanoseconds duration were applied from two sources at different carrier frequencies of 10 and 3.7 GHz. The repetition rate was 100 pps, and the duration of train pulses lasted from 10 s to twice 8 min. The effects were studied on the central nervous system, by labelling brain inflammation marker GFAP and by performing different behavioural tests: rotarod, T-maze, beam-walking, open-field, and avoidance test. Long-time survival was measured in animals repeatedly exposed, and anatomopathological analysis was performed on animals sacrificed at two years of life or at death if earlier. One group was sham exposed.Few effects were observed on behaviour. With acute exposure, an avoidance reflex was shown at very high, thermal level (22 W/kg); GFAP was increased some days after exposure. Most importantly, with repeated exposures, survival time was 4-month shorter in the exposed group, with eleven animals exhibiting a large sub-cutaneous tumour, compared to two in the sham group. A residual X-ray exposure was also present in the beam (0.8 Gy), which is not a bias for the observed result.High power microwaves below thermal level in average, can increase cancer incidence and decrease survival time in rats, without clear effects on behaviour. The parameters of this effect need to be explored further, and a more precise dosimetry to be performed.

Published
2020

17. TNAP as a therapeutic target for cardiovascular calcification - a discussion of its pleiotropic functions in the body

Author

Claudia, Goettsch, Agnieszka, Strzelecka-Kiliszek, Laurence, Bessueille, Thibaut, Quillard, Laura, Mechtouff, Slawomir, Pikula, Emmanuelle, Canet-Soulas, Jose Luis, Millan, Caroline, Fonta, David, Magne, Universitätsklinikum RWTH Aachen - University Hospital Aachen [Aachen, Germany] (UKA), RWTH Aachen University, Nencki Institute of Experimental Biology, Polska Akademia Nauk = Polish Academy of Sciences (PAN), 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), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université Bretagne Loire (UBL), 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), 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), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), 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)-Hospices Civils de Lyon (HCL), Sanford Burnham Prebys Medical Discovery Institute, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CarMeN, laboratoire, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), 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-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 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 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, and Centre National de la Recherche Scientifique (CNRS)

Subjects
Inflammation, Therapeutic target, [SDV]Life Sciences [q-bio], Reviews, Cardiovascular Agents, Arteries, Alkaline Phosphatase, equipment and supplies, Substrate Specificity, [SDV] Life Sciences [q-bio], Tissue non-specific alkaline phosphatase, Animals, Humans, AcademicSubjects/MED00200, Enzyme Inhibitors, Phosphorylation, Erratum, Cardiovascular calcification, Vascular Calcification, Signal Transduction, Inhibition
Abstract

Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP’s functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo., Graphical Abstract

Published
2020

18. Radiosynthesis of [18F]AV1451 in pharmaceutical conditions and its biological characteristics

Author

Marie Bernadette Delisle, Caroline Fonta, A.S. Salabert, Mathieu Alonso, Najat Loukh, Pierre Payoux, Charlotte Fontan, Mathieu Tafani, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie Pathologique, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre de Microscopie Électronique Appliquée à la Biologie (CMEAB), Toulouse Réseau Imagerie-Genotoul ( TRI-Genotoul), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Hôpital de Rangueil, Department of Nuclear Medicine, and National Institute of Neurosurgery

Subjects
Radiation, Chromatography, Stability study, Chemistry, [SCCO.NEUR]Cognitive science/Neuroscience, Radiosynthesis, Plasma protein binding, Blood proteins, In vitro, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Biochemistry, Human plasma, Biological property, Yield (chemistry), ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery
Abstract

In this study, we describe the radiosynthesis of [18F]AV1451 in terms of its pharmaceutical quality and characterise its physical and biological properties. We performed an in vitro serum stability study in fresh human plasma and a plasma protein binding study. The radiochemical yield was 24% (decay corrected), and the product met all regulatory quality requirements. We found that this compound is stable in fresh human plasma and binds tightly to plasma proteins, especially lipoproteins.

Published
2017

19. Analysis of vascular homogeneity and anisotropy on high-resolution primate brain imaging

Author

Romain Guibert, Franck Plouraboué, Pol Kennel, and Caroline Fonta

Subjects
Physics, Radiological and Ultrasound Technology, Blood volume, Voxel-based morphometry, Grey matter, computer.software_genre, Lobe, 030218 nuclear medicine & medical imaging, Functional imaging, 03 medical and health sciences, 0302 clinical medicine, Nuclear magnetic resonance, medicine.anatomical_structure, Neurology, Neuroimaging, Voxel, Functional neuroimaging, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, computer, Neuroscience, 030217 neurology & neurosurgery
Abstract

Using a systematic investigation of brain blood volume, in high-resolution synchrotron 3D images of microvascular structures within cortical regions of a primate brain, we challenge several basic questions regarding possible vascular bias in high-resolution functional neuroimaging. We present a bilateral comparison of cortical regions, where we analyze relative vascular volume in voxels from 150 to 1000 lm side lengths in the white and grey matter. We show that, if voxel size reaches a scale smaller than 300 mm, the vascular volume can no longer be considered homogeneous, either within one hemisphere or in bilateral comparison between samples. We demonstrate that voxel size influences the comparison between vessel-relative volume distributions depending on the scale considered (i.e., hemisphere, lobe, or sample). Furthermore, we also investigate how voxel anisotropy and orientation can affect the apparent vascular volume, in accordance with actual fMRI voxel sizes. These findings are discussed from the various perspectives of high-resolution brain functional imaging

Published
2017

20. TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.

Author

Claudia, Goettsch, Agnieszka, Strzelecka-Kiliszek, Laurence, Bessueille, Thibaut, Quillard, Laura, Mechtouff, Slawomir, Pikula, Emmanuelle, Canet-Soulas, Millan, Jose Luis, Caroline, Fonta, and David, Magne

Subjects
ATHEROSCLEROSIS, CALCIFICATION, ADENINE nucleotides, VITAMIN B6, ALKALINE phosphatase, ARTERIAL calcification
Abstract

Cardiovascular calcification (CVC) is associated with increased morbidity and mortality. It develops in several diseases and locations, such as in the tunica intima in atherosclerosis plaques, in the tunica media in type 2 diabetes and chronic kidney disease, and in aortic valves. In spite of the wide occurrence of CVC and its detrimental effects on cardiovascular diseases (CVD), no treatment is yet available. Most of CVC involve mechanisms similar to those occurring during endochondral and/or intramembranous ossification. Logically, since tissue-nonspecific alkaline phosphatase (TNAP) is the key-enzyme responsible for skeletal/dental mineralization, it is a promising target to limit CVC. Tools have recently been developed to inhibit its activity and preclinical studies conducted in animal models of vascular calcification already provided promising results. Nevertheless, as its name indicates, TNAP is ubiquitous and recent data indicate that it dephosphorylates different substrates in vivo to participate in other important physiological functions besides mineralization. For instance, TNAP is involved in the metabolism of pyridoxal phosphate and the production of neurotransmitters. TNAP has also been described as an anti-inflammatory enzyme able to dephosphorylate adenosine nucleotides and lipopolysaccharide. A better understanding of the full spectrum of TNAP's functions is needed to better characterize the effects of TNAP inhibition in diseases associated with CVC. In this review, after a brief description of the different types of CVC, we describe the newly uncovered additional functions of TNAP and discuss the expected consequences of its systemic inhibition in vivo. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
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21. Brain Segmentation from Super-Resolved Magnetic Resonance Images

Author

Ahmad Diab, Muriel Mescam, Denis Kouame, Adrian Basarab, Farah Bazzi, Juan D. Rodriguez-Callejas, Hassan Amoud, Caroline Fonta, Omar Falou, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Lebanese University [Beirut] (LU), Azm Center for Biotechnology Research, Lebanese University [Beirut] (LU)-Agence universitaire de la Francophonie (Beyrouth, Lebanon), Laboratoire Modélisation et Sûreté des Systèmes (LM2S), 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), Doctoral School of Sciences and Technology [Lebanese University], American University of Culture & Education (AUCE), CoMputational imagINg anD viSion (IRIT-MINDS), 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), Association of Azm w Saade (AWS) and Doctoral School of Science and Technology - Tripoli, Liban, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Agence universitaire de la Francophonie (Beyrouth, Lebanon)-Lebanese University [Beirut] (LU), Université Toulouse Capitole (UT Capitole), Université Fédérale Toulouse Midi-Pyrénées-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse Capitole (UT Capitole), Fonta, Caroline, Université de Toulouse (UT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), 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)-Toulouse Mind & Brain Institut (TMBI), and Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole)

Subjects
Point spread function, Deblurring, Computer science, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, 0302 clinical medicine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Brain segmentation, Segmentation, structural MRI, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, Ground truth, marmoset, medicine.diagnostic_test, business.industry, segmentation, Single image super-resolution, Magnetic resonance imaging, Pattern recognition, Fast algorithm, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.anatomical_structure, ICV, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, cerebral aging
Abstract

International audience; The objective of this work is to investigate the ability of a 2D super resolution (SR) technique in 3D restoration and enhancement of brain magnetic resonance images to facilitate the study of cerebral aging bio-markers. The SR method exploits the joint properties of the system point spread function and sub-sampling operators to derive a fast algorithm. Brain images of the common marmoset, Callithrix jacchus, acquired at different ages are used in this study. The evaluation of the final outcome of our method is done by computing the intracranial volume from the segmentation of the brain compartments: gray matter, white matter and cerebrospinal fluid. Results show that the deblurring of the images improves the segmentation process with respect to the ground truth. However, super resolution leads to the best quantification of the intracranial volume when compared to the deblurred and the original images. Therefore, despite its sub-optimality, the 2D SR method provides reliable results for improving the quality of the images used in the study of aging in terms of precision of reconstruction and computational time.

Published
2019

22. Sulcal pattern variation in extant human endocasts

Author

Anna Catherina Oettle, Albert-Neels Van Schoor, Laurent Risser, Caroline Fonta, Jakobus Hoffman, Edwin John De Jager, Amélie Beaudet, Muriel Mescam, South African Nuclear Energy Corporation [Pretoria] (NECSA), University of Pretoria [South Africa], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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), Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-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)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Histology, Temporal lobe, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Imaging, Three-Dimensional, Extant taxon, medicine, Image Processing, Computer-Assisted, Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, ComputingMilieux_MISCELLANEOUS, Fossil Record, Crania, biology, Fossils, [SCCO.NEUR]Cognitive science/Neuroscience, Skull, Brain, Paleontology, Cell Biology, Human brain, Original Articles, X-Ray Microtomography, biology.organism_classification, Biological Evolution, 030104 developmental biology, medicine.anatomical_structure, Human evolution, Frontal lobe, Anatomy, Cartography, 030217 neurology & neurosurgery, Geology, Endocast, Software, Developmental Biology
Abstract

Our knowledge of human brain evolution primarily relies on the interpretation of palaeoneurological evidence. In this context, an endocast or replica of the inside of the bony braincase can be used to reconstruct a timeline of cerebral changes that occurred during human evolution, including changes in topographic extension and structural organisation of cortical areas. These changes can be tracked by identifying cerebral imprints, particularly cortical sulci. The description of these crucial landmarks in fossil endocasts is, however, challenging. High-resolution imaging techniques in palaeoneurology offer new opportunities for tracking detailed endocranial neural characteristics. In this study, we use high-resolution imaging techniques to document the variation in extant human endocranial sulcal patterns for subsequent use as a platform for comparison with the fossil record. We selected 20 extant human crania from the Pretoria Bone Collection (University of Pretoria, South Africa), which were detailed using X-ray microtomography at a spatial resolution ranging from 94 to 123 μm (isometric). We used Endex to extract, and Matlab to analyse the cortical imprints on the endocasts. We consistently identified superior, middle and inferior sulci on the frontal lobe; and superior and inferior sulci on the temporal lobe. We were able to label sulci bordering critical functional areas such as Broca's cap. Mapping the sulcal patterns on extant endocasts is a prerequisite for constructing an atlas which can be used for automatic sulci recognition.

Published
2019

23. Chronic recurrent multifocal osteomyelitis in children with hypophosphatasia explained by anti-inflammatory nucleotidase activity of tissue nonspecific alkaline phosphatase in mesenchymal and hematopoietic cells

Author

Marie Gleizes, David Magne, Caroline Fonta, Jamal Alaeddine El, Charles Dumontet, Etienne Mornet, Cylia Mansouri, Juna Como, José Luis Millán, Laurence Bessueille, Eva-Laure Matera, René Buchet, Anne Briolay, 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 de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), 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 Hospitalier de Versailles André Mignot (CHV), Sanford Burnham Medical Research Institute, La Jolla, Matériaux d'intérêt biologique, and Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Pathology, medicine.medical_specialty, Nucleotidase activity, medicine.drug_class, business.industry, [SDV]Life Sciences [q-bio], Mesenchymal stem cell, Chronic recurrent multifocal osteomyelitis, Hypophosphatasia, General Medicine, medicine.disease, Anti-inflammatory, 3. Good health, Haematopoiesis, medicine, Tissue-nonspecific Alkaline Phosphatase, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

24. Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter

Author

Lionel G. Nowak, Simon P. Perrier, Caroline Fonta, Marie Gleizes, Université Paris Nanterre - UFR Sciences sociales et administration (UPN SSA), Université Paris Nanterre (UPN), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), ROSITO, Maxime, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Central Nervous System, Adenosine, Time Factors, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Models, Neurological, Stimulation, 030204 cardiovascular system & hematology, In Vitro Techniques, Synaptic Transmission, A1 receptor, 03 medical and health sciences, Adenosine A1 receptor, chemistry.chemical_compound, Cellular and Molecular Neuroscience, piriform cortex, 0302 clinical medicine, Neuronal Plasticity and Repair, Postsynaptic potential, Physiology (medical), Piriform cortex, medicine, Animals, Neurotransmitter, Original Research, Neuronal Plasticity, Receptor, Adenosine A1, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, oscillation, presynaptic inhibition, Electric Stimulation, short‐term plasticity, Olfactory bulb, Adenosine A1 Receptor Agonists, Mice, Inbred C57BL, chemistry, Synaptic plasticity, Biophysics, Female, short-term plasticity, 030217 neurology & neurosurgery, medicine.drug
Abstract

International audience; We examined the effect of adenosine and of adenosine A1 receptor blockage on short‐term synaptic plasticity in slices of adult mouse anterior piriform cortex maintained in vitro in an in vivo‐like ACSF. Extracellular recording of postsynaptic responses was performed in layer 1a while repeated electrical stimulation (5‐pulse‐trains, frequency between 3.125 and 100 Hz) was applied to the lateral olfactory tract. Our stimulation protocol was aimed at covering the frequency range of oscillatory activities observed in the olfactory bulb in vivo. In control condition, postsynaptic response amplitude showed a large enhancement for stimulation frequencies in the beta and gamma frequency range. A phenomenological model of short‐term synaptic plasticity fitted to the data suggests that this frequency‐dependent enhancement can be explained by the interplay between a short‐term facilitation mechanism and two short‐term depression mechanisms, with fast and slow recovery time constants. In the presence of adenosine, response amplitude evoked by low‐frequency stimulation decreased in a dose‐dependent manner (IC50 = 70 μmol/L). Yet short‐term plasticity became more dominated by facilitation and less influenced by depression. Both changes compensated for the initial decrease in response amplitude in a way that depended on stimulation frequency: compensation was strongest at high frequency, up to restoring response amplitudes to values similar to those measured in control condition. The model suggested that the main effects of adenosine were to decrease neurotransmitter release probability and to attenuate short‐term depression mechanisms. Overall, these results suggest that adenosine does not merely inhibit neuronal activity but acts in a more subtle, frequency‐dependent manner.

Published
2019

25. Multi-angle TOF MR brain angiography of the common marmoset

Author

Nathalie Vayssiere, Muriel Mescam, Caroline Fonta, J. Brossard, Neurochirurgie [Hôpital Gui de Chauliac], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.diagnostic_test, biology, Computer science, business.industry, Marmoset, Image processing, Magnetic resonance imaging, Context (language use), Pattern recognition, Image segmentation, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Robustness (computer science), biology.animal, Digital image processing, Angiography, medicine, Computer vision, Artificial intelligence, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract

The relation between normal and pathological aging and the cerebrovascular component is still unclear. In this context, the common marmoset, which has the advantage of enabling longitudinal studies over a reasonable timeframe, appears as a good pre-clinical model. However, there is still a lack of quantitative information on the macrovascular structure of the marmoset brain. In this paper, we investigate the potentiality of multi-angle TOF MR angiography using a 3T MRI scanner to perform morphometric analysis of the marmoset brain vasculature. Our image processing pipeline greatly relies on the use of multiscale vesselness enhancement filters to help extract the 3D macrovasculature and perform subsequent morphometric calculations. Although multi-angle acquisition does not improve morphometric analysis significantly as compared to single-angle acquisition, it improves the network extraction by increasing the robustness of image processing algorithms.

Published
2017

26. Analysis of vascular homogeneity and anisotropy on high-resolution primate brain imaging

Author

Pol, Kennel, Caroline, Fonta, Romain, Guibert, and Franck, Plouraboué

Subjects
Cerebral Cortex, Callithrix, Organ Size, Immunohistochemistry, Magnetic Resonance Imaging, White Matter, Functional Laterality, Cerebral Angiography, Imaging, Three-Dimensional, Microvessels, Animals, Anisotropy, Female, Gray Matter, Research Articles
Abstract

Using a systematic investigation of brain blood volume, in high‐resolution synchrotron 3D images of microvascular structures within cortical regions of a primate brain, we challenge several basic questions regarding possible vascular bias in high‐resolution functional neuroimaging. We present a bilateral comparison of cortical regions, where we analyze relative vascular volume in voxels from 150 to 1000 μm side lengths in the white and grey matter. We show that, if voxel size reaches a scale smaller than 300 µm, the vascular volume can no longer be considered homogeneous, either within one hemisphere or in bilateral comparison between samples. We demonstrate that voxel size influences the comparison between vessel‐relative volume distributions depending on the scale considered (i.e., hemisphere, lobe, or sample). Furthermore, we also investigate how voxel anisotropy and orientation can affect the apparent vascular volume, in accordance with actual fMRI voxel sizes. These findings are discussed from the various perspectives of high‐resolution brain functional imaging. Hum Brain Mapp 38:5756–5777, 2017. © 2017 Wiley Periodicals, Inc.

Published
2017

27. Radiosynthesis of [

Author

Anne-Sophie, Salabert, Charlotte, Fontan, Caroline, Fonta, Mathieu, Alonso, Najat, Loukh, Marie Bernadette, Delisle, Mathieu, Tafani, and Pierre, Payoux

Subjects
Fluorine Radioisotopes, Radioligand Assay, Lipoproteins, Humans, Reproducibility of Results, Neurodegenerative Diseases, Spectrophotometry, Ultraviolet, Blood Proteins, Radiopharmaceuticals, Chromatography, High Pressure Liquid, Carbolines, Protein Binding
Abstract

In this study, we describe the radiosynthesis of [

Published
2016

28. Loss of ferritin-positive microglia relates to increased iron, RNA oxidation, and dystrophic microglia in the brains of aged male marmosets

Author

Juan D. Rodriguez-Callejas, Eberhard Fuchs, Abraham Rosas-Arellano, Caroline Fonta, Claudia Perez-Cruz, Daniel Cuervo-Zanatta, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology, and Center of Research and Advance Studies

Subjects
Male, 0106 biological sciences, Aging, medicine.medical_specialty, Iron, Phagocytosis, Hippocampus, Inflammation, Hippocampal formation, Ferroxidase activity, 010603 evolutionary biology, 01 natural sciences, [SCCO]Cognitive science, Internal medicine, medicine, Animals, 0501 psychology and cognitive sciences, 050102 behavioral science & comparative psychology, ComputingMilieux_MISCELLANEOUS, Ecology, Evolution, Behavior and Systematics, Cerebral Cortex, biology, Microglia, Chemistry, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Neurodegeneration, Callithrix, medicine.disease, Ferritin, Endocrinology, medicine.anatomical_structure, Ferritins, biology.protein, RNA, Animal Science and Zoology, medicine.symptom
Abstract

Microglia are cells that protect brain tissue from invading agents and toxic substances, first by releasing pro-inflammatory cytokines, and thereafter by clearing tissue by phagocytosis. Microglia express ferritin, a protein with ferroxidase activity capable of storing iron, a metal that accumulates in brain during aging. Increasing evidence suggests that ferritin plays an important role in inflammation. However, it is not known if ferritin/iron content can be related to the activation state of microglia. To this end, we aimed to delineate the role of ferritin in microglia activation in a non-human primate model. We analyzed brains of male marmosets and observed an increased density of ferritin+ microglia with an activated phenotype in hippocampus and cortex of old marmosets (mean age 11.25 ± 0.70 years) compared to younger subjects. This was accompanied by an increased number of dystrophic microglia in old marmosets. However, in aged subjects (mean age 16.83 ± 2.59 years) the number of ferritin+ microglia was decreased compared to old ones. Meanwhile, the content of iron in brain tissue and cells with oxidized RNA increased during aging in all hippocampal and cortical regions analyzed. Abundant amoeboid microglia were commonly observed surrounding neurons with oxidized RNA. Notably, amoeboid microglia were arginase1+ and IL-10+, indicative of a M2 phenotype. Some of those M2 cells also presented RNA oxidation and a dystrophic phenotype. Therefore, our data suggest that ferritin confers protection to microglia in adult and old marmosets, while in aged subjects the decline in ferritin and the increased amount of iron in brain tissue may be related to the increased number of cells with oxidized RNA, perhaps precluding the onset of neurodegeneration.

Published
2019

29. TNAP, an Essential Player in Membrane Lipid Rafts of Neuronal Cells

Author

Caroline Fonta, Florence Baychelier, Myriam Ermonval, Stratégies antivirales, Institut Pasteur [Paris], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Caroline Fonta, László Négyessy, Institut Pasteur [Paris] (IP), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Fonta, Caroline, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microenvironment, extra cellular matrix, MESH: Membrane Lipids / metabolism, [SDV]Life Sciences [q-bio], Phosphatase, TNAP activity, MESH: Cell Membrane / metabolism, Extracellular matrix, 03 medical and health sciences, Membrane Lipids, 0302 clinical medicine, Membrane Microdomains, MESH: Neurons / ultrastructure, Extracellular, Animals, Humans, MESH: Neurons / metabolism, Ectonucleotidase, MESH: Animals, Protein Interaction Maps, neuronal function, Cytoskeleton, Lipid raft, MESH: Extracellular Matrix / metabolism, 030304 developmental biology, MESH: Membrane Microdomains / metabolism, Neurons, 0303 health sciences, protein network, MESH: Humans, MESH: Protein Interaction Maps / physiology, Chemistry, Cell Membrane, Phosphomonoesterase, MESH: Alkaline Phosphatase / physiology, Alkaline Phosphatase, Cell biology, Extracellular Matrix, [SDV] Life Sciences [q-bio], Alkaline phosphatase, lipids (amino acids, peptides, and proteins), 030217 neurology & neurosurgery
Abstract

International audience; The tissue non-specific alkaline phosphatase (TNAP) is a glycosyl-phosphatidylinositol (GPI) anchored glycoprotein which exists under different forms and is expressed in different tissues. As the other members of the ecto-phosphatase family, TNAP is targeted to membrane lipid rafts. Such micro domains enriched in particular lipids, are involved in cell sorting, are in close contact with the cellular cytoskeleton and play the role of signaling platform. In addition to its location in functional domains, the extracellular orientation of TNAP and the fact this glycoprotein can be shed from plasma membranes, contribute to its different phosphatase activities by acting as a phosphomonoesterase on various soluble substrates (inorganic pyrophosphate -PPi-, pyridoxal phosphate -PLP-, phosphoethanolamine -PEA-), as an ectonucleotidase on nucleotide-phosphate and presumably as a phosphatase able to dephosphorylate phosphoproteins and phospholipids associated to cells or to extra cellular matrix. More and more data accumulate on an involvement of the brain TNAP both in physiological and pathological situations. This review will summarize what is known and expected from the TNAP localization in lipid rafts with a particular emphasis on the role of a neuronal microenvironment on its potential function in the central nervous system.

Published
2015

30. COVID-19 inactivated and non-replicating viral vector vaccines induce regulatory training phenotype in human monocytes under epigenetic control

Author

Mateus da Silva Matias Antunes, Fabricia Heloisa Cavicchioli Sugiyama, Humberto Doriguetto Gravina, Ricardo Cardoso Castro, Francisco Javier Romero Mercado, Julia Oliveira de Lima, Caroline Fontanari, and Fabiani Gai Frantz

Subjects
vaccine, COVID-19, trained immunity, monocyte, epigenetic, Microbiology, QR1-502
Abstract

BackgroundTrained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response.MethodsTherefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated in vitro with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training.ResultsWhen challenged in vitro, monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the IL6 and IL10 genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the IL6, IL10, TNF, and CCL2 genes.ConclusionsOur findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.

Published
2023
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31. Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP)

Author

Caroline Fonta, László Négyessy, Caroline Fonta, and László Négyessy

Subjects
Alkaline phosphatase
Abstract

Phosphatases, such as TNAP are fundamental in regulating the roles of cellular, and consequently numerous body functions. TNAP is a ubiquitous enzyme with a wide spectrum of substrates and specificity. Regulation at the cellular level and the lack of TNAP activity is a lethal condition. Recent findings of a highly specific regional, laminar and subcellular localization of TNAP in the cerebral cortex indicates that in addition to its metabolic and skeletal functions, TNAP also plays a role in regulating cerebral functions, most probably cognition. In fact, TNAP disturbance could result in complex diseases such as epilepsy, developmental retardation and Alzheimer's disease. Available data suggest that, regarding brain functions, TNAP is a potentially important target of clinical research. This book aims to provide an overview of our current understanding of the functions of TNAP in the brain and on other tissues and organs.

Published
2015

32. Nanofibrils to Track Phosphatase Activity on Live Cells

Author

Caroline Fonta, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010405 organic chemistry, Chemistry, General Chemical Engineering, [SCCO.NEUR]Cognitive science/Neuroscience, Biochemistry (medical), Phosphatase, General Chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, 0104 chemical sciences, 3. Good health, Materials Chemistry, Environmental Chemistry, Alkaline phosphatase
Abstract

In this issue of Chem, Xu and colleagues have developed a new method of detecting ectophosphatase activity in cells maintained in culture, allowing the spatio-temporal pattern of alkaline phosphatase activity to be followed at the single-cell level.

Published
2016

33. Cognitive impairment in a young marmoset reveals lateral ventriculomegaly and a mild hippocampal atrophy: a case report

Author

Pascal Girard, E. Bonté, Amirouche Sadoun, Caroline Fonta, Kuzma Strelnikov, Service hématologie Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, medicine.medical_specialty, Pathology, Audiology, Hippocampus, Article, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Neuroimaging, biology.animal, medicine, Animals, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Behavior, Animal, medicine.diagnostic_test, biology, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, Marmoset, Callithrix, Magnetic resonance imaging, Cognition, biology.organism_classification, medicine.disease, Magnetic Resonance Imaging, Radiography, Female, Abnormality, Cognition Disorders, business, Photic Stimulation, 030217 neurology & neurosurgery, Ventriculomegaly
Abstract

The number of studies that use the common marmoset (Callithrix jacchus) in various fields of neurosciences is increasing dramatically. In general, animals enter the study when their health status is considered satisfactory on the basis of classical clinical investigations. In behavioral studies, variations of score between individuals are frequently observed, some of them being considered as poor performers or outliers. Experimenters rarely consider the fact that it could be related to some brain anomaly. This raises the important issue of the reliability of such classical behavioral approaches without using complementary imaging, especially in animals lacking striking external clinical signs. Here we report the case of a young marmoset which presented a set of cognitive impairments in two different tasks compared to other age-matched animals. Brain imaging revealed a patent right lateral ventricular enlargement with a mild hippocampal atrophy. This abnormality could explain the cognitive impairments of this animal. Such a case points to the importance of complementing behavioral studies by imaging explorations to avoid experimental bias.

Published
2015

34. A New Approach to Model Confined Suspensions Flows in Complex Networks: Application to Blood Flow

Author

Franck Plouraboué, Caroline Fonta, Romain Guibert, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), and Université Toulouse III - Paul Sabatier - UT3 (FRANCE)

Subjects
Mécanique des fluides, General Chemical Engineering, 0206 medical engineering, Phase separation, 02 engineering and technology, Catalysis, Blood rheology, 03 medical and health sciences, Theoretical physics, 0302 clinical medicine, Complex geometry, Statistical physics, Conservation of mass, Network model, Mathematics, Confined suspensions, Topological complexity, Conservation law, Network models, Neurosciences, Complex network, 020601 biomedical engineering, Apparent viscosity, Flow (mathematics), Parametric model, Fahræus–Lindquist effect, 030217 neurology & neurosurgery
Abstract

The modeling of blood flows confined in micro-channels or micro-capillary beds depends on the interactions between the cell-phase, plasma and the complex geometry of the network. In the case of capillaries or channels having a high aspect ratio (their longitudinal size is much larger than their transverse one), this modeling is much simplified from the use of a continuous description of fluid viscosity as previously proposed in the literature. Phase separation or plasma skimming effect is a supplementary mechanism responsible for the relative distribution of the red blood cell’s volume density in each branch of a given bifurcation. Different models have already been proposed to connect this effect to the various hydrodynamics and geometrical parameters at each bifurcation. We discuss the advantages and drawbacks of these models and compare them to an alternative approach for modeling phase distribution in complex channels networks. The main novelty of this new formulation is to show that albeit all the previous approaches seek for a local origin of the phase segregation phenomenon, it can arise from a global non-local and nonlinear structuration of the flow inside the network. This new approach describes how elementary conservation laws are sufficient principles (rather than the complex parametric models previously proposed) to provide non local phase separation. Spatial variations of the hematocrit field thus result from the topological complexity of the network as well as nonlinearities arising from solving a new free boundary problem associated with the flux and mass conservation. This network model approach could apply to model blood flow distribution either on artificial micro-models, micro-fluidic networks, or realistic reconstruction of biological micro-vascular networks.

Published
2009

35. Synchrotron microbeam radiation therapy for rat brain tumor palliation—influence of the microbeam width at constant valley dose

Author

Géraldine Le Duc, Jean A. Laissue, Audrey Bouchet, Elke Bräuer-Krisch, Jean Boutonnat, Raphaël Serduc, Luc Renaud, Alberto Bravin, François Estève, Sukhena Sarun, Caroline Fonta, E.A. Siegbahn, Jenny Spiga, European Synchrotron Radiation Facility (ESRF), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Pathology Institute, University of Bern, RFMQ, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Service d'Imagerie par Résonance Magnétique (IRM), CHU Grenoble, Serduc, R, Bouchet, A, Braeuer-Krisch, E, Laissue Jean, A, Spiga, J, Sarun, S, Bravin, A, Fonta, C, Renaud, L, Boutonnat, J, Siegbahn Erik, A, Esteve, F, and Le Duc, G

Subjects
Male, Gliosarcoma, Necrosis, medicine.medical_treatment, FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA), 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Therapeutic index, rat brain, Cell Line, Tumor, medicine, Animals, Radiology, Nuclear Medicine and imaging, Irradiation, Radiotherapy, Radiological and Ultrasound Technology, Brain Neoplasms, business.industry, Chemistry, Therapeutic effect, Brain, Dose-Response Relationship, Radiation, Microbeam, medicine.disease, Rats, Inbred F344, Rats, Radiation therapy, 030220 oncology & carcinogenesis, Toxicity, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Nuclear medicine, business, Monte Carlo Method, microbeam radiation therapy, Neoplasm Transplantation, Synchrotrons
Abstract

International audience; To analyze the effects of the microbeam width (25, 50 and 75 microm) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MRT50, MRT75), each using two orthogonally intersecting arrays of either 25, 50 or 75 microm wide microbeams, all spaced 211 microm on center, were tested. For each configuration, peak entrance doses of 860, 480 and 320 Gy, respectively, were calculated to produce an identical valley dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days after radiation treatment, 42 rats were killed to evaluate histopathologically the extent of tumor necrosis, and the presence of proliferating tumors cells and tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48 days for MRT25, 50 and 75, respectively. The combination of the highest entrance doses (860 Gy per array) with 25 microm wide beams (MRT25) resulted in a cumulative valley dose of 36 Gy and was excessively toxic, as it led to early death of all normal rats and of approximately 50% of tumor-bearing rats. The short survival times, particularly of rats in the MRT25 group, restricted adequate observance of the therapeutic effect of the method on tumor-bearing rats. However, microbeams of 50 microm width led to the best median survival time after 9L gliosarcoma MRT treatment and appeared as the better compromise between tumor control and normal brain toxicity compared with 75 microm or 25 microm widths when used with a 211 microm on-center distance. Despite very high radiation doses, the tumors were not sterilized; viable proliferating tumor cells remained present at the tumor margin. This study shows that microbeam width and peak entrance doses strongly influence tumor responses and normal brain toxicity, even if valley doses are kept constant in all groups. The use of 50 microm wide microbeams combined with moderate peak doses resulted in a higher therapeutic ratio.

Published
2009

36. Rediscovering TNAP in the Brain: A Major Role in Regulating the Function and Development of the Cerebral Cortex

Author

Caroline, Fonta, Pascal, Barone, Laia, Rodriguez Martinez, and László, Négyessy

Subjects
Cerebral Cortex, Brain Diseases, Animals, Brain, Humans, Hypophosphatasia, Nerve Tissue, Alkaline Phosphatase
Abstract

The presence of alkaline phosphatase (AP) activity in the neural tissue has been described decades ago. However, only recent studies clarified the isotype, regional distribution and subcellular localization of the AP expressed in the cerebral cortex of diverse mammalian species including the human. In the primate brain the discovery that the bone AP isotype (TNAP) is expressed provided the opportunity of a deeper understanding of the role of this enzyme in neuronal functions based on the knowledge acquired by studying the role of the enzyme in hypophosphatasia, mostly in bone mineralization. TNAP exhibits widespread substrate specificity and, in the brain, it is potentially involved in the regulation of molecules which play fundamental roles in signal transmission and development. In light of these observations, the localization of TNAP in the human cerebral cortex is of high significance when considering that epilepsy is often diagnosed in hypophosphatasia. Here we overview our results on the identification of TNAP in the primate cerebral cortex: TNAP exhibits a noticeably high activity in the synapses and nodes of Ranvier, is specifically present in layer 4 of the sensory cortices and additionally in layer 5 of prefrontal, temporal and other associational areas in human. Our studies also indicate that bone AP activity depends on the level of sensory input and that its developmental time-course exhibits characteristic regional differences. The relevance of our findings regarding human cortical physiology and brain disorders are discussed.

Published
2015

37. Signal Transduction Pathways of TNAP: Molecular Network Analyses

Author

László, Négyessy, Balázs, Györffy, János, Hanics, Mihály, Bányai, Caroline, Fonta, and Fülöp, Bazsó

Subjects
Neurons, Animals, Cluster Analysis, Humans, Gene Regulatory Networks, Protein Interaction Maps, Alkaline Phosphatase, Synaptic Transmission, Databases, Chemical, Signal Transduction
Abstract

Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

Published
2015

38. Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex

Author

Caroline Fonta, Lionel G. Nowak, Dávid Czégé, Benoît Rosay, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
medicine.medical_specialty, Sodium channel, [SCCO.NEUR]Cognitive science/Neuroscience, Biology, Pharmacology, Levamisole, Inhibitory postsynaptic potential, Adenosine, 3. Good health, Cortex (botany), Electrophysiology, [SCCO]Cognitive science, Endocrinology, Internal medicine, medicine, Alkaline phosphatase, Premovement neuronal activity, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

Tissue non-specific alkaline phosphatase (TNAP) may be involved in the synthesis of GABA and adenosine, which are the main inhibitory neurotransmitters in cortex. We explored this putative TNAP function through electrophysiological recording (local field potential ) in slices of mouse somatosensory cortex maintained in vitro . We used tetramisole , a well documented TNAP inhibitor, to block TNAP activity. We expected that inhibiting TNAP with tetramisole would lead to an increase of neuronal response amplitude, owing to a diminished availability of GABA and/or adenosine. Instead, we found that tetramisole reduced neuronal response amplitude in a dose-dependent manner. Tetramisole also decreased axonal conduction velocity. Levamisole had identical effects. Several control experiments demonstrated that these actions of tetramisole were independent from this compound acting on TNAP. In particular, tetramisole effects were not stereo-specific and they were not mimicked by another inhibitor of TNAP, MLS-0038949 . The decrease of axonal conduction velocity and preliminary intracellular data suggest that tetramisole blocks voltage-dependent sodium channels . Our results imply that levamisole or tetramisole should not be used with the sole purpose of inhibiting TNAP in living excitable cells as it will also block all processes that are activity-dependent. Our data and a review of the literature indicate that tetramisole may have at least four different targets in the nervous system. We discuss these results with respect to the neurological side effects that were observed when levamisole and tetramisole were used for medical purposes, and that may recur nowadays due to the recent use of levamisole and tetramisole as cocaine adulterants.

Published
2015

39. Signal Transduction Pathways of TNAP: Molecular Network Analyses

Author

Mihály Bányai, Balazs Gyorffy, László Négyessy, János Hanics, Fülöp Bazsó, Caroline Fonta, Department of Anatomy, Histology and Embryology, Semmelweis University [Budapest], Research Group for Pediatrics and Nephrology, Hungarian Academy of Sciences and Semmelweis University, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pyramidal Neuron, Neuronal signal transduction, Neurodegeneration, Purinergic receptor, Biology, Neurotransmission, medicine.disease, Bioinformatics, Molecular network, Second messenger system, medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal transduction, Neuroscience, ComputingMilieux_MISCELLANEOUS
Abstract

Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer’s disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.

Published
2015

40. Multiple Functions of MSCA-1/TNAP in Adult Mesenchymal Progenitor/Stromal Cells

Author

Caroline Fonta, Jean Galitzky, David Estève, Anne Bouloumié, René Buchet, David Magne, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Métabolisme, Enzymes et Mécanismes Moléculaires (MEM²), 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 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)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, lcsh:Internal medicine, Stromal cell, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Cellular differentiation, Mesenchymal stem cell, Clinical uses of mesenchymal stem cells, Cell Biology, Review Article, Bioinformatics, Cell biology, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, medicine, Alkaline phosphatase, Bone marrow, Progenitor cell, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:RC31-1245, business, Molecular Biology, Stem cell transplantation for articular cartilage repair
Abstract

International audience; Our knowledge about mesenchymal stem cells has considerably grown in the last years. Since the proof of concept of the existence of such cells in the 70s by Friedenstein et al., a growing mass of reports were conducted for a better definition of these cells and for the reevaluation from the term “mesenchymal stem cells” to the term “mesenchymal stromal cells (MSCs).” Being more than a semantic shift, concepts behind this new terminology reveal the complexity and the heterogeneity of the cells grouped in MSC family especially as these cells are present in nearly all adult tissues. Recently, mesenchymal stromal cell antigen-1 (MSCA-1)/tissue nonspecific alkaline phosphatase (TNAP) was described as a new cell surface marker of MSCs from different tissues. The alkaline phosphatase activity of this protein could be involved in wide range of MSC features described below from cell differentiation to immunomodulatory properties, as well as occurrence of pathologies. The present review aims to decipher and summarize the role of TNAP in progenitor cells from different tissues focusing preferentially on brain, bone marrow, and adipose tissue.

Published
2015

41. Rediscovering TNAP in the Brain: A Major Role in Regulating the Function and Development of the Cerebral Cortex

Author

Pascal Barone, László Négyessy, Laia Rodriguez Martinez, Caroline Fonta, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Histology and Embryology, and Semmelweis University [Budapest]

Subjects
0303 health sciences, Node of Ranvier, Synaptic cleft, [SCCO.NEUR]Cognitive science/Neuroscience, Hypophosphatasia, Sensory system, Anatomy, Biology, Neurotransmission, Subcellular localization, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Cerebral cortex, medicine, Neuroscience, 030217 neurology & neurosurgery, Function (biology), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

The presence of alkaline phosphatase (AP) activity in the neural tissue has been described decades ago. However, only recent studies clarified the isotype, regional distribution and subcellular localization of the AP expressed in the cerebral cortex of diverse mammalian species including the human. In the primate brain the discovery that the bone AP isotype (TNAP) is expressed provided the opportunity of a deeper understanding of the role of this enzyme in neuronal functions based on the knowledge acquired by studying the role of the enzyme in hypophosphatasia, mostly in bone mineralization. TNAP exhibits widespread substrate specificity and, in the brain, it is potentially involved in the regulation of molecules which play fundamental roles in signal transmission and development. In light of these observations, the localization of TNAP in the human cerebral cortex is of high significance when considering that epilepsy is often diagnosed in hypophosphatasia. Here we overview our results on the identification of TNAP in the primate cerebral cortex: TNAP exhibits a noticeably high activity in the synapses and nodes of Ranvier, is specifically present in layer 4 of the sensory cortices and additionally in layer 5 of prefrontal, temporal and other associational areas in human. Our studies also indicate that bone AP activity depends on the level of sensory input and that its developmental time-course exhibits characteristic regional differences. The relevance of our findings regarding human cortical physiology and brain disorders are discussed.

Published
2015

42. Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors

Author

Charlotte Fontan, Mathieu Tafani, Carine Pestourie, Djilali Adel, A.S. Salabert, Pierre Payoux, Mathieu Alonso, Caroline Fonta, Hafid Belhadj-Tahar, Imagerie cérébrale et handicaps neurologiques (ICHN), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse], Centre de recherche cerveau et cognition (CERCO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie in vivo de l'expression des gènes, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie cérébrale et handicaps neurologiques, CHU Toulouse [Toulouse]-Hôpital Rangueil, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut des sciences du cerveau de Toulouse. (ISCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Fluorine Radioisotopes, Cancer Research, Pathology, medicine.medical_specialty, Metabolic Clearance Rate, Phencyclidine, Pharmacology, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Memantine, In vivo, medicine, Animals, Tissue Distribution, Radiology, Nuclear Medicine and imaging, 030304 developmental biology, 0303 health sciences, Chemistry, [SCCO.NEUR]Cognitive science/Neuroscience, Radiosynthesis, Brain, Colocalization, Rats, 3. Good health, Kinetics, Isotope Labeling, Positron-Emission Tomography, Autoradiography, Molecular Medicine, NMDA receptor, Radiopharmaceuticals, 030217 neurology & neurosurgery, Ex vivo, Immunostaining, medicine.drug
Abstract

The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory transmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [(18)F]-fluoroethylnormemantine ([(18)F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state.Radiosynthesis was carried out using the Raytest® SynChrom RD fluorination module. Affinity of this new compound was determined by competition assay. We ran a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS® software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining.Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145 MBq and a specific activity above 355 GBq/μmol. Affinity assessment allowed us to determine [(19)F]-FNM IC50 at 6.1 10(-6)M. [(18)F]-FMN concentration gradually increased in the brain, stabilizing at 40 minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [(18)F]-FNM (r=0.622, p0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine.[(18)F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders.

Published
2015

43. Areal and Subcellular Localization of the Ubiquitous Alkaline Phosphatase in the Primate Cerebral Cortex: Evidence for a Role in Neurotransmission

Author

László Négyessy, Pascal Barone, Caroline Fonta, and Luc Renaud

Subjects
Cognitive Neuroscience, Sensory system, Neurotransmission, Biology, Somatosensory system, Synaptic Transmission, gamma-Aminobutyric acid, Cellular and Molecular Neuroscience, Species Specificity, medicine, Animals, Tissue Distribution, Sensory cortex, Cerebral Cortex, Neurons, Callithrix, Somatosensory Cortex, Alkaline Phosphatase, Macaca mulatta, Rats, Monocular deprivation, medicine.anatomical_structure, Cerebral cortex, Cats, Alkaline phosphatase, Neuroscience, Subcellular Fractions, medicine.drug
Abstract

The ubiquitous enzyme TNAP (tissue non-specific alkaline phosphatase) is found in numerous tissues such as liver, kidney and bone, but little attention has been paid to its expression and role in the brain. Observations in TNAP-KO mice, which analyzed the role of this enzyme in osteogenesis, had suggested that TNAP might be involved in GABA neurotransmission. Apart from its presence in endothelial cells, here we show a specific and strong alkaline phosphatase (AP) activity in the neuropile, matching the pattern of thalamo-cortical innervation in layer 4 of the primate sensory cortices (visual, auditory and somatosensory). Such a pattern is also evident in rodents and carnivores, making AP a powerful marker of primary sensory areas. Remarkably, AP activity is regulated by sensory experience as demonstrated by monocular deprivation paradigms in monkeys. The areal and laminar distribution of AP activity matches that of the GAD(65), the GABA synthesizing enzyme found in presynatic terminals. As our electron microscopic investigations indicate that AP is found at the neuronal membranes and in synaptic contacts, it is proposed that the neuronal AP isoform (NAP), may be a key enzyme in regulating neurotransmission and could therefore play an important role in developmental plasticity and activity-dependent cortical functions.

Published
2004

44. TNAP activity is localized at critical sites of retinal neurotransmission across various vertebrate species

Author

László Négyessy, Zsuzsanna Szepessy, Caroline Fonta, Roland Nitschke, Gabor Baksa, Ákos Lukáts, Tamás Kovács-Öller, Anna W. Roe, Béla Völgyi, Lajos Balogh, Ágoston Szél, Alexandra Varga, Orsolya Kántor, Anna Enzsoly, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Histology and Embryology, and Semmelweis University [Budapest]

Subjects
Histology, Guinea Pigs, Biology, Neurotransmission, Synaptic Transmission, Pathology and Forensic Medicine, Guinea pig, chemistry.chemical_compound, Mice, Dogs, Species Specificity, Cricetinae, medicine, Animals, Humans, Zebrafish, Saimiri, Retina, Sheep, Mesocricetus, [SCCO.NEUR]Cognitive science/Neuroscience, Ferrets, Retinal, Cell Biology, Anatomy, biology.organism_classification, Inner plexiform layer, Alkaline Phosphatase, Cell biology, Rats, medicine.anatomical_structure, chemistry, Cats, sense organs, Rabbits, Golden hamster, Retinal Neurons
Abstract

Evidence is emerging with regard to the role of tissue non-specific alkaline phosphatase (TNAP) in neural functions. As an ectophosphatase, this enzyme might influence neural activity and synaptic transmission in diverse ways. The localization of the enzyme in known neural circuits, such as the retina, might significantly advance an understanding of its role in normal and pathological functioning. However, the presence of TNAP in the retina is scarcely investigated. Our multispecies comparative study (zebrafish, cichlid, frog, chicken, mouse, rat, golden hamster, guinea pig, rabbit, sheep, cat, dog, ferret, squirrel monkey, human) using enzyme histochemistry and Western blots has shown the presence of TNAP activity in the retina of several mammalian species, including humans. Although the TNAP activity pattern varies across species, we have observed the following trends: (1) in all investigated species (except golden hamster), retinal vessels display TNAP activity; (2) TNAP activity consistently occurs in the photoreceptor layer; (3) in majority of the investigated species, marked TNAP activity is present in the outer and inner plexiform layers. In zebrafish, frog, chicken, guinea pig, and rat, TNAP histochemistry has revealed several sublayers of the inner plexiform layer. Frog, golden hamster, guinea pig, mouse, and human retinas possess a subpopulation of amacrine cells positively staining for TNAP activity. The expression of TNAP in critical sites of retinal signal transmission across a wide range of species suggests its fundamental, evolutionally conserved role in vision.

Published
2014

45. Effect of monocular deprivation on NMDAR1 immunostaining in ocular dominance columns of the marmoset Callithrix jacchus

Author

Michel Imbert, Caroline Fonta, and Catherine Chappert

Subjects
Proline, genetic structures, Physiology, Receptors, N-Methyl-D-Aspartate, Ocular dominance, Immunoenzyme Techniques, Vision, Monocular, biology.animal, medicine, Animals, Visual Pathways, Dominance, Cerebral, Visual Cortex, New World monkey, biology, Marmoset, Callithrix, biology.organism_classification, eye diseases, Sensory Systems, Neuronal tracing, Monocular deprivation, Visual cortex, medicine.anatomical_structure, Animals, Newborn, Thalamic Nuclei, Autoradiography, Sensory Deprivation, Neuroscience, Ocular dominance column
Abstract

We previously showed that immunoreactivity to N-Methyl-D-aspartate (NMDA) receptors in primary visual cortex of Callithrix jacchus is regulated by visual activity during the second and third postnatal months (Fonta et al., 1997). The purpose of the present study was to show that the columnar pattern of high and low NMDAR1 immunoreactivity observed in monocularly deprived animals corresponds to ocular dominance columns linked to the nondeprived and deprived eye, respectively. We compared cortical distribution of NMDAR1 receptors and the projection zones of thalamic afferents, revealed by transneuronal transport of tritiated proline, in 2-month-old, either monocularly deprived or control, marmosets. The data show that ocular dominance columns exist in 2-month-old marmosets and that a 2-week monocular deprivation by means of eyelid suture leads to a modification of the thalamo-cortical afferents organization. Experiments of neuronal tracing and immunohistochemistry performed on the same animals demonstrated that cortical domains with decreased NMDAR1 level correspond to the deprived eye columns. These investigations, coupled to the previous results, strongly suggest that the NMDA receptors, regulated by visual activity, are involved in the refining of ocular dominance columns in the primary visual cortex of juvenile marmoset.

Published
2000

46. The cell cycle gene SKP1 is regulated by light in postnatal rat brain

Author

Michel Mathieu, Emmanuelle Uro-Coste, Marie-Bernadette Delisle, Eric Perret, Daniel Caput, Michel Imbert, and Caroline Fonta

Subjects
Light, Molecular Sequence Data, Cell Cycle Proteins, Biology, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, Neuroplasticity, Skp1, medicine, Animals, Humans, Rats, Long-Evans, Visual Pathways, Northern blot, S-Phase Kinase-Associated Proteins, Molecular Biology, Cyclin, Neuronal Plasticity, Base Sequence, Kinase, Brain, Cell cycle, Rats, Visual cortex, medicine.anatomical_structure, Animals, Newborn, Gene Expression Regulation, Neuroscience, Ocular dominance column
Abstract

During the early postnatal phase of high neuronal plasticity, an altered visual input leads to great modifications of visual cortex organization [Y. Fregnac, M. Imbert, Development of neuronal selectivity in primary visual cortex of cat, Physiol. Rev., 64 (1984) 375–434; D.H. Hubel, T.N. Wiesel, S. LeVay, Plasticity of ocular dominance columns in monkey striate cortex, Philos. Trans. R. Soc. London, Ser. B, 278 (1977) 377–409.]. We used refined differential screening of an organized cDNA library to identify the genes that may participate in this plasticity. We isolated a candidate plasticity gene encoding for a 163 aa protein that is closely related to the human and yeast Skp1p, a key factor in cell cycle progression [C. Bai, K. Hofman, L. Ma, M. Goebl, J.W. Harper, S.J. Elledge, SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box, Cell, 86 (1996) 263–274; C. Connelly, P. Hieter, Budding yeast SKP1 encodes an evolutionary conserved kinetochore protein required for cell cycle progression, Cell, 86 (1996) 275–285; H. Zhang, R. Kobayashi, K. Galaktionov, D. Beach, p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase, Cell, 82 (1995) 915–925.]. Northern blot analysis showed that the expression of SKP1 (Skp1p gene) dramatically decreased after 2 h of light stimulation in the visual cortex of young dark-reared rats. This down regulation lasted at least 72 h. It was specific for the critical period as we did not observe any significant regulation of SKP1 mRNA by light in adult dark-reared rat brain. The down regulation was observed in the superior colliculus but also in the frontal cortex and in the hippocampus. The fact that this down regulation was not restricted to the visual system, suggested that it could be produced by dark rearing-induced hormonal changes. The significance of SKP1 expression in the brain and its regulation are discussed.

Published
1998

47. CD18 controls the development and activation of monocyte-to-macrophage axis during chronic schistosomiasis

Author

Camila O. S. Souza, Jefferson Elias-Oliveira, Marcella R. Pastore, Caroline Fontanari, Vanessa F. Rodrigues, Vanderlei Rodriguez, Luiz G. Gardinassi, and Lúcia H. Faccioli

Subjects
β2 integrin, monocytes, proliferation, alternatively activated macrophages, schistosomiasis, Immunologic diseases. Allergy, RC581-607
Abstract

Schistosomiasis is a neglected tropical disease caused by worms of the genus Schistosoma spp. The progression of disease results in intense tissue fibrosis and high mortality rate. After egg deposition by adult worms, the inflammatory response is characterized by the robust activation of type 2 immunity. Monocytes and macrophages play critical roles during schistosomiasis. Inflammatory Ly6Chigh monocytes are recruited from the blood to the inflammatory foci and differentiate into alternatively activated macrophages (AAMs), which promote tissue repair. The common chain of β2-integrins (CD18) regulates monocytopoiesis and mediates resistance to experimental schistosomiasis. There is still limited knowledge about mechanisms controlled by CD18 that impact monocyte development and effector cells such as macrophages during schistosomiasis. Here, we show that CD18low mice chronically infected with S. mansoni display monocyte progenitors with reduced proliferative capacity, resulting in the accumulation of the progenitor cell denominated proliferating-monocyte (pMo). Consequently, inflammatory Ly6Chigh and patrolling Ly6Clow monocytes are reduced in the bone marrow and blood. Mechanistically, low CD18 expression decreases Irf8 gene expression in pMo progenitor cells, whose encoded transcription factor regulates CSFR1 (CD115) expression on the cell surface. Furthermore, low CD18 expression affects the accumulation of inflammatory Ly6Chigh CD11b+ monocytes in the liver while the adoptive transference of these cells to infected-CD18low mice reduced the inflammatory infiltrate and fibrosis in the liver. Importantly, expression of Il4, Chil3l3 and Arg1 was downregulated, CD206+PD-L2+ AAMs were reduced and there were lower levels of IL-10 in the liver of CD18low mice chronically infected with S. mansoni. Overall, these findings suggest that CD18 controls the IRF8-CD115 axis on pMo progenitor cells, affecting their proliferation and maturation of monocytes. At the same time, CD18 is crucial for the appropriate polarization and function of AAMs and tissue repair during chronic schistosomiasis.

Published
2022
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48. N‐methyl‐D‐aspartate subunit R1 involvement in the postnatal organization of the primary visual cortex of Callithrix jacchus

Author

Caroline Fonta, Michel Imbert, and Catherine Chappert

Subjects
Neocortex, biology, General Neuroscience, Long-term potentiation, biology.organism_classification, Callithrix, Postnatal age, Visual cortex, medicine.anatomical_structure, medicine, Developmental plasticity, NMDA receptor, Neuroscience, New World monkey
Abstract

It has been demonstrated that the primary visual cortex is highly sensitive to manipulations of the visual environment during a specific, early, postdevelopmental period: the critical period. Pharmacological studies have shown that N-methyl-D-aspartate (NMDA) receptors are involved in the plasticity of the visual cortex just as they are involved in the induction of long-term potentiation (LTP), another activity-dependent form of plasticity. The setting up of synaptic connectivity in the neocortex may rely on LTP-like mechanisms. By using immunohistochemistry techniques, we tested the hypothesis of the role of subunit R1 of NMDA (NMDAR1) receptors in the thalamocortical afferent segregation into ocular-dominance columns in the New World monkey,Callithrix jacchus.We employed early and short (2 weeks) monocular-deprivation periods at different ages of postnatal development (17, 46, 67, 107, and 188 postnatal days). We observed heterogeneous distribution of NMDAR1 in the layer IVC receiving the thalamic inputs if the deprivation was realized between the ages of 46 and 107 days. Layers IVCa and IVCb were involved differently as a function of the deprivation age. The striped pattern lost its differential intensity with the postnatal age. These results are compared with the ocular-dominance pattern evolution described in other works on this primate. They provide evidence of the NMDAR1 role in the modular organization, within time limits, during the postnatal development of the primary visual cortex. J. Comp. Neurol.

Published
1997

49. On the normalization of cerebral blood flow

Author

Romain Guibert, François Estève, Caroline Fonta, Franck Plouraboué, Centre National de la Recherche Scientifique - CNRS (FRANCE), European Synchrotron Radiation Facility - ESRF (FRANCE), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Institut National Polytechnique de Toulouse - INPT (FRANCE), Institut de mécanique des fluides de Toulouse (IMFT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 6, Rayonnement synchrotron et recherche médicale, Grenoble Institut des Neurosciences (GIN), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Pathology, Mécanique des fluides, Hemodynamics, microcirculation, Blood volume, Perfusion scanning, brain imaging, Brain imaging, Brief Communication, 030218 nuclear medicine & medical imaging, Microcirculation, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Brain perfusion, Internal medicine, medicine, Animals, Cerebral perfusion pressure, Computed tomography, Blood Volume, business.industry, brain perfusion, Neurosciences, Brain, computed tomography, Callithrix, Neurology, Cerebral blood flow, Cerebrovascular Circulation, Cardiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Perfusion, 030217 neurology & neurosurgery, Tomography, Emission-Computed
Abstract

International audience; Cerebral blood flow (CBF) is the most common parameter for the quantification of brain's function. Literature data indicate a widespread dispersion of values that might be related to some differences in the measurement conditions that are not properly taken into account in CBF evaluation. Using recent high-resolution imaging of the complete cortical microvasculature of primate brain, we perform extensive numerical evaluation of the cerebral perfusion. We show that blood perfusion associated with intravascular tracers should be normalized by the surface of the voxel rather than by its volume and we consistently test this result on the available literature data.

Published
2013

50. Automatic dendrite spines detection from X-ray tomography volumes

Author

Grégoire Malandain, Lazlo Negyessy, Caroline Fonta, Xavier Descombes, Rajmund Mosko, Morphologie et Images (MORPHEME), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Hungarian Academy of Sciences (MTA), The Swiss Light Source (SLS) (SLS-PSI), Paul Scherrer Institute (PSI), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), and Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
musculoskeletal diseases, Dendritic spine, Dendrite, 02 engineering and technology, Iterative reconstruction, Hough transform, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Medial axis, 0202 electrical engineering, electronic engineering, information engineering, medicine, Computer vision, Segmentation, Mathematics, business.industry, Image segmentation, musculoskeletal system, medicine.anatomical_structure, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], 020201 artificial intelligence & image processing, Artificial intelligence, Tomography, business, 030217 neurology & neurosurgery, ACM: I.: Computing Methodologies
Abstract

International audience; We consider the problem of dendritic spine detection from X-ray micro-tomographic volumes that allow huge volume of tissue visualization. To compensate for the noise in data that induces false positives in the spine detection process, we first segment the dendrites. This segmentation is obtained by computing the medial axis and approximating the results by segments obtained with a 3D Hough transform. Dendrites are then reconstructed and a spine mask is obtained using the typical diameter of dendrites and distance between spine and dendrites. A point process is then optimized on this mask, thus providing the spine detection.

Published
2013

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