Glutamatergic synapse in autism: a complex story for a complex disorder.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
22
07
2022
accepted:
28
10
2022
revised:
12
10
2022
pubmed:
27
11
2022
medline:
11
2
2023
entrez:
26
11
2022
Statut:
ppublish
Résumé
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD. Thus, our objective was to characterize glutamate dysfunctions in adult subjects with ASD by quantifying (1) glutamate levels in the cingulate cortex and periphery using proton magnetic resonance spectroscopy and metabolomics, and (2) mGluR5 brain density in this population and in a validated animal model of ASD (prenatal exposure to valproate) at developmental stages corresponding to childhood and adolescence in humans using positron emission tomography. No modifications in cingulate Glu levels were observed between individuals with ASD and controls further supporting the difficulty to evaluate modifications in excitatory transmission using spectroscopy in this population, and the complexity of its glutamate-related changes. Our imaging results showed an overall increased density in mGluR5 in adults with ASD, that was only observed mostly subcortically in adolescent male rats prenatally exposed to valproic acid, and not detected in the stage corresponding to childhood in the same animals. This suggest that clinical changes in mGluR5 density could reflect the adaptation of the glutamatergic dysfunctions occurring earlier rather than being key to the pathophysiology of ASD.
Identifiants
pubmed: 36434055
doi: 10.1038/s41380-022-01860-9
pii: 10.1038/s41380-022-01860-9
doi:
Substances chimiques
Glutamic Acid
3KX376GY7L
Valproic Acid
614OI1Z5WI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
801-809Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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