Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism.

Autor: Gholipour P; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran., Ebrahimi Z; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran., Mohammadkhani R; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran., Ghahremani R; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran.; Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran., Salehi I; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran., Sarihi A; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran.; Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran., Komaki A; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran.; Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran., Karimi SA; Neurophysiology Research Center, Hamadan University of Medical Sciences, Shahid Fahmideh Street, Hamadan, 65178/518, Iran. seyedasaad.karimi@utoronto.ca.; Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. seyedasaad.karimi@utoronto.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jun 07; Vol. 14 (1), pp. 13168. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1038/s41598-024-63728-y
Abstrakt: Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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