Group I and group II metabotropic glutamate receptors are upregulated in the synapses of infant rats prenatally exposed to valproic acid.
Autism spectrum disorder
LY341495
MTEP
Ultrasonic vocalization
Valproic acid
mGlu1 receptors
mGlu2/3 receptors
mGlu5 receptors
Journal
Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
01
08
2023
accepted:
23
08
2023
medline:
13
11
2023
pubmed:
14
9
2023
entrez:
14
9
2023
Statut:
ppublish
Résumé
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and restricted/stereotyped behavior. Prenatal exposure to valproic acid (VPA) is associated with an increased risk of developing ASD in humans and autistic-like behaviors in rodents. Increasing evidence indicates that dysfunctions of glutamate receptors at synapses are associated with ASD. In the VPA rat model, an involvement of glutamate receptors in autism-like phenotypes has been suggested; however, few studies were carried out on metabotropic glutamate (mGlu) receptors. We examined the protein expression levels of group I (mGlu1 and mGlu5) and group II (mGlu2/3) mGlu receptors in rats prenatally exposed to VPA and evaluated the effect of mGlu receptor modulation on an early autism-like phenotype in these animals. We used western blotting analysis on synaptosomes obtained from forebrain of control and VPA rats at different ages (postnatal day P13, 35, 90) and carried out ultrasonic vocalization (USV) emission test in infant control and VPA rats. The expression levels of all these receptors were significantly increased in infant VPA rats. No changes were detected in adolescent and adult rats. An acute treatment with the preferential mGlu2/3 antagonist, LY341495, attenuated the impairment in the USV emission in VPA rats. No effect was observed after a treatment with the mGlu5 selective antagonist, MTEP. Our findings demonstrate that the expression of group I and group II mGlu receptors is upregulated at synapses of infant VPA rats and suggest that mGlu2/3 receptor modulation may have a therapeutic potential in ASD.
Identifiants
pubmed: 37707611
doi: 10.1007/s00213-023-06457-w
pii: 10.1007/s00213-023-06457-w
pmc: PMC10640443
doi:
Substances chimiques
Valproic Acid
614OI1Z5WI
Receptors, Metabotropic Glutamate
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2617-2629Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. The Author(s).
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