| Title: |
Behavioral and striatal alterations with aging in two mouse models of autism spectrum disorders ; Altérations comportementales et striatales au cours du vieillissement dans deux modèles murins de troubles du spectre autistique |
| Authors: |
Thabault, Mathieu |
| Contributors: |
Laboratoire de neurosciences expérimentales et cliniques U 1084 (LNEC Poitiers ); Université de Poitiers = University of Poitiers (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM); Université de Poitiers; Mohamed Jaber; Laurie Galvan |
| Source: |
https://theses.hal.science/tel-04143407 ; Médecine humaine et pathologie. Université de Poitiers, 2022. Français. ⟨NNT : 2022POIT2277⟩. |
| Publisher Information: |
CCSD |
| Publication Year: |
2022 |
| Collection: |
Université de Poitiers: Publications de nos chercheurs.ses (HAL) |
| Subject Terms: |
Patch-Clamp; Dendritic arborization; Dorsolateral striatum; Aging; Cntnap2; Shank3; Autism spectrum disorders; Arborisation dendritique; Striatum dorsolatéral; Vieillissement; Troubles du spectre autistique; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| Description: |
Autism spectrum disorders are neurodevelopmental disorders affecting one person in 160 around the world. They are characterized by communication and social impairments, associated with a restricted pattern of interests and behaviors. Alterations in GABA levels have been highlighted in patients with autism spectrum disorders (ASD), but mechanisms underlying these alterations remain unclear. One of the key structure in ASD physiopathology is the striatum, as it is involved in motor, associative and cognitive functions, all three altered in ASD. In this thesis work, two transgenic mouse models of ASD have been used (Shank3∆C/∆C and Cntnap2-/-) as they display a strong face validity. Indeed, both mutations are found in syndromic and non-syndromic ASD patients. This PhD thesis are about the evolution of ASD motor symptoms with aging as well as the evolution of related striatal alterations, in three experimental groups: 10weeks, 20weeks, 40weeks, with both males and females. Results exposed here show the presence of motor stereotypies at different stages, worsening with aging. Patch-clamp recordings of DLS MSNs show dysfunctions in GABAergic transmission, evolving with aging. To go further, we examined the neuronal morphology as well as the functionality of PV interneurons, which are the main source of GABA onto the MSNs, with an optogenetic approach. Finally, a chemogenetic approach allowed us to study the phenotypic restoration in ASD mice models. The work presented here allow to characterize striatal dysfunctions in our models, and to establish a timeline for their evolution. ; Les troubles du spectre autistique sont un ensemble de troubles neurodéveloppementaux affectant 1 personne sur 160 dans le monde et se traduisant par des troubles sociaux et de communication, ainsi qu’un ensemble restreint d’intérêts et de comportements. Des altérations dans les niveaux de GABA ont été mises en évidences chez les patients atteints de troubles du spectre autistique (TSA) depuis plusieurs décennies déjà, mais les mécanismes ... |
| Document Type: |
doctoral or postdoctoral thesis |
| Language: |
French |
| Relation: |
NNT: 2022POIT2277 |
| Availability: |
https://theses.hal.science/tel-04143407; https://theses.hal.science/tel-04143407v1/document; https://theses.hal.science/tel-04143407v1/file/2022-Thabault-Mathieu-These.pdf |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.D081F211 |
| Database: |
BASE |