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5 results on '"AMX-19-IET-004"'

1. NAPB and developmental and epileptic encephalopathy: Description of the electroclinical profile associated with a novel pathogenic variant

Author

Cécile Mignon‐Ravix, Florence Riccardi, Géraldine Daquin, Pierre Cacciagli, Sylvie Lamoureux‐Toth, Laurent Villard, Nathalie Villeneuve, Florence Molinari, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurophysiologie clinique [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de ressources biologiques Tissus ADN Cellules [Hôpital de la Timone - APHM] (CRB TAC), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Henri Duffaut (Avignon), Laboratoire de Génétique Moléculaire [Hôpital de la Timone - APHM], Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM], and A*Midex : AMX-19-IET-004

Subjects
Electroencephalogram, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Seizures, SNARE, [SCCO.NEUR]Cognitive science/Neuroscience, NAPB, Neurology (clinical), SNAP, Whole Exome Sequencing, Developmental and Epileptic Encephalopathies
Abstract

International audience; Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. DEE are genetically heterogeneous, and the proteins involved play roles in multiple pathways such as synaptic transmission, metabolism, neuronal development or maturation, transcriptional regulation, and intracellular trafficking. We performed whole exome sequencing on a consanguineous family with three children presenting an early onset (

Published
2023

2. APOE4 drives inflammation in human astrocytes via TAGLN3 repression and NF-κB activation

Author

Arnaud, Laurie, Benech, Philippe, Greetham, Louise, Stephan, Delphine, Jimenez, Angélique, Jullien, Nicolas, García-González, Laura, Tsvetkov, Philipp, Devred, François, Sancho-Martinez, Ignacio, Izpisua Belmonte, Juan Carlos, Baranger, Kévin, Rivera, Santiago, Nivet, Emmanuel, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), FAES farma, Altos Labs, Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), ANR-21-CE17-0047,TRANS3,TAGLN3, un nouveau régulateur de la neuroinflammation: un biomarqueur et une cible thérapeutique dans la maladie d'Alzheimer(2021), LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), and This work was supported by the CNRS and Aix Marseille Universite´.The work was also supported by the DHUNE Center of Excellence and a CoEN grant (to S.R. and E.N.), by the ‘‘FONDATION ALZHEIMER’’ (to S.R. and E.N.), by ‘‘Fondation Vaincre Alzheimer’’ (FR-19052 to E.N.), by ‘‘La Fondation NRJ-Institut de France’’ to E.N., by l’Agence Nationale de la Recherche (ANR) (ANR-21-CE17-0047-01 to E.N.), and by a CoEN grant to S.R. and E.N. L.G.-G. was supported by an ANR grant (MAD5) to S.R. and also by grants from the Fondation pour la Recherche Me´dicale FRM FDT201904008423 and by a Fondation Vaincre Alzheimer international travel grant. This work has received support from the French government under the Programme Investissements d’Avenir, Initiative d’Excellence d’Aix-Marseille Universite´ via A*Midex (AMX-19-IET-004) and ANR (ANR17-EURE-0029) funding.

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Apolipoprotein E4 (APOEε4) is the major allelic risk factor for late-onset sporadic Alzheimer’s disease (sAD). Inflammation is increasingly considered as critical in sAD initiation and progression. Identifying brain molecular mechanisms that could bridge these two risk factors remain unelucidated. Leveraging induced pluripotent stem cell (iPSC)-based strategies, we demonstrate that APOE controls inflammation in human astrocytes by regulating Transgelin 3 (TAGLN3) expression and, ultimately, nuclear factor kB (NF-kB) activation. We uncover that APOE4 specifically downregulates TAGLN3, involving histone deacetylases activity, which results in low-gradechronicinflammationandhyperactivatedinflammatoryresponses.Weshow that APOE4 exerts a dominant negative effect to prime astrocytes toward a pro-inflammatory state that is pharmacologically reversible by TAGLN3 supplementation. We further confirm that TAGLN3 is downregulated in the brainofpatientswithsAD.OurfindingshighlighttheAPOE-TAGLN3-NF-kBaxisregulatingneuroinflammation in human astrocytes and reveal TAGLN3 as amolecular target to modulate neuroinflammation, as well as a potential biomarker for AD.

Published
2022

3. Correction: Targeted Tshz3 deletion in corticostriatal circuit components segregates core autistic behaviors

Author

Xavier Caubit, Paolo Gubellini, Pierre L. Roubertoux, Michèle Carlier, Jordan Molitor, Dorian Chabbert, Mehdi Metwaly, Pascal Salin, Ahmed Fatmi, Yasmine Belaidouni, Lucie Brosse, Lydia Kerkerian-Le Goff, Laurent Fasano, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de psychologie cognitive (LPC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), This work has received support from the French government under the Programme 'Investissements d’Avenir', Initiative d’Excellence d’Aix-Marseille Université via A*Midex funding (NeuroMarseille Institute, AMX-19-IET-004, MarMaRa Institute, AMX-19-IET-007). We wish to thank the IBDM mouse facility. This work was supported by the Fédération pour la Recherche sur le Cerveau (FRC) (to L.F.), the Centre National de la Recherche Scientifique (CNRS) and Aix-Marseille University. D.C. and J.M. were supported by PhD grants from the MESRI (Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation)., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), ANR-17-EURE-0029,nEURo*AMU,Marseille NeuroSchool, une formation d'excellence(2017), ANR-17-CE16-0030,TSHZ3inASD,Rôle de TSHZ3 dans le développement et la fonction de systèmes neuronaux impliqués dans les troubles du spectre autistique(2017), Gubellini, Paolo, Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID, Marseille NeuroSchool, une formation d'excellence - - nEURo*AMU2017 - ANR-17-EURE-0029 - EURE - VALID, and Rôle de TSHZ3 dans le développement et la fonction de systèmes neuronaux impliqués dans les troubles du spectre autistique - - TSHZ3inASD2017 - ANR-17-CE16-0030 - AAPG2017 - VALID

Subjects
Cellular and Molecular Neuroscience, Psychiatry and Mental health, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biological Psychiatry
Abstract

International audience; We previously linked TSHZ3 haploinsufficiency to autism spectrum disorder (ASD) and showed that embryonic or postnatal Tshz3 deletion in mice results in behavioral traits relevant to the two core domains of ASD, namely social interaction deficits and repetitive behaviors. Here, we provide evidence that cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) are two main and complementary players in the TSHZ3-linked ASD syndrome. In the cerebral cortex, TSHZ3 is expressed in CPNs and in a proportion of GABAergic interneurons, but not in cholinergic interneurons or glial cells. In the striatum, TSHZ3 is expressed in all SCINs, while its expression is absent or partial in the other main brain cholinergic systems. We then characterized two new conditional knockout (cKO) models generated by crossing Tshz3 flox/flox with Emx1-Cre (Emx1-cKO) or Chat-Cre (Chat-cKO) mice to decipher the respective role of CPNs and SCINs. Emx1-cKO mice show altered excitatory synaptic transmission onto CPNs and impaired plasticity at corticostriatal synapses, with neither cortical neuron loss nor abnormal layer distribution. These animals present social interaction deficits but no repetitive patterns of behavior. Chat-cKO mice exhibit no loss of SCINs but changes in the electrophysiological properties of these interneurons, associated with repetitive patterns of behavior without social interaction deficits. Therefore, dysfunction in either CPNs or SCINs segregates with a distinct ASD behavioral trait. These findings provide novel insights onto the implication of the corticostriatal circuitry in ASD by revealing an unexpected neuronal dichotomy in the biological background of the two core behavioral domains of this disorder.

Published
2022

4. Preparing to React: A Behavioral Study on the Interplay between Proactive and Reactive Action Inhibition

Author

Ficarella, Stefania, Desantis, Andrea, Zenon, Alexandre, Burle, Boris, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), DTIS, ONERA [Salon], ONERA, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), AMX-19-IET-004, ANR-17-EURE-0029,nEURo*AMU,Marseille NeuroSchool, une formation d'excellence(2017), ANR-18-CE10-0001,BLADE,Décodage et suivi des états cognitifs d'un opérateur(2018), European Project: 241077,EC:FP7:ERC,ERC-2009-StG,PRORECONT(2010), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
compatibility effect, partial error, [SCCO.NEUR]Cognitive science/Neuroscience, proactive, Neurosciences. Biological psychiatry. Neuropsychiatry, motor inhibition, Article, inhibitory control, EMG, [SCCO.PSYC]Cognitive science/Psychology, reactive, motor preparation, action inhibition, RC321-571
Abstract

International audience; Motor preparation, based on one's goals and expectations, allows for prompt reactions to stimulations from the environment. Proactive and reactive inhibitory mechanisms modulate this preparation and interact to allow a flexible control of responses. In this study, we investigate these two control mechanisms with an ad hoc cued Go/NoGo Simon paradigm in a within-subjects design, and by measuring subliminal motor activities through electromyographic recordings. Go cues instructed participants to prepare a response and wait for target onset to execute it (Go target) or inhibit it (NoGo target). Proactive inhibition keeps the prepared response in check, hence preventing false alarms. Preparing the cue-coherent effector in advance speeded up responses, even when it turned out to be the incorrect effector and reactive inhibition was needed to perform the action with the contralateral one. These results suggest that informative cues allow for the investigation of the interaction between proactive and reactive action inhibition. Partial errors' analysis suggests that their appearance in compatible conflict-free trials depends on cue type and prior preparatory motor activity. Motor preparation plays a key role in determining whether proactive inhibition is needed to flexibly control behavior, and it should be considered when investigating proactive/reactive inhibition.

Published
2021

5. Assessing model-based inferences in decision making with single-trial response time decomposition

Author

Gabriel Weindel, Boris Burle, F.-Xavier Alario, Royce Anders, Laboratoire de psychologie cognitive (LPC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Institute of Language, Communication and the Brain (ILCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), AMX-19-IET-004, ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), and ANR-16-CONV-0002,ILCB,ILCB: Institute of Language Communication and the Brain(2016)

Subjects
Cognitive model, media_common.quotation_subject, Decision Making, Experimental and Cognitive Psychology, Interval (mathematics), Models, Psychological, Machine learning, computer.software_genre, 050105 experimental psychology, Interpretation (model theory), 03 medical and health sciences, 0302 clinical medicine, Developmental Neuroscience, Reaction Time, Humans, Quality (business), 0501 psychology and cognitive sciences, General Psychology, media_common, Interpretability, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, Response time, Cognition, Motor processes, [SCCO.PSYC]Cognitive science/Psychology, Artificial intelligence, business, Psychology, computer, 030217 neurology & neurosurgery
Abstract

Decision-making models based on evidence accumulation processes (the most prolific one being the drift-diffusion model – DDM) are widely used to draw inferences about latent psychological processes from chronometric data. While the observed goodness of fit in a wide range of tasks supports the model’s validity, the derived interpretations have yet to be sufficiently cross-validated with other measures that also reflect cognitive processing. To do so, we recorded electromyographic (EMG) activity along with response times (RT), and used it to decompose every RT into two components: a pre-motor (PMT) and motor time (MT). These measures were mapped to the DDM's parameters, thus allowing a test, beyond quality of fit, of the validity of the model’s assumptions and their usual interpretation. In two perceptual decision tasks, performed within a canonical task setting, we manipulated stimulus contrast, speed-accuracy trade-off, and response force, and assessed their effects on PMT, MT, and RT. Contrary to common assumptions, these three factors consistently affected MT. DDM parameter estimates of non-decision processes are thought to include motor execution processes, and they were globally linked to the recorded response execution MT. However, when the assumption of independence between decision and non-decision processes was not met, in the fastest trials, the link was weaker. Overall, the results show a fair concordance between model-based and EMG-based decompositions of RTs, but also establish some limits on the interpretability of decision model parameters linked to response execution.

Published
2021

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