ArticleCNS neuroscience & therapeutics2025
Prenatal Valproic Acid Exposure Impairs Offspring Cognition Through Disturbing Interneuron Development.
Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Role of Hippocampal Interneuron Migration in Neurodevelopmental Disorders: A Systematic Review.Hippocampus · 2026Pooled it
- Genetic and pharmacological evidence linking CB1R signaling to hippocampal GABAergic dysfunction in ASD mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
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Authors and funding
6 authors.
Funding
Abstract
aimsValproic acid (VPA) exposure during the gestational period has been found to impair the cognition of the offspring. The study aimed to investigate whether VPA leads to offspring cognitive impairment through disturbing interneuron development.
methodsPregnant mice were injected with VPA peritoneally to establish the prenatal VPA exposure model. Cortical interneurons were labeled with Rosa26-EYFP/- reporter mice activated by Nkx2.1-Cre. Interneuron subtypes both in the cortex and the hippocampus were detected by immunofluorescence. A battery of behavioral tests was conducted on postnatal Day 28 to assess the cognition and anxiety of the offspring. RNA-Seq analysis was performed to investigate the underlying molecular mechanisms.
resultsWe found that after the exposure to VPA, all the groups of the male offspring exerted anxiety. When VPA injection was performed on gestational Day 12.5, the memory of the offspring was impaired. Mechanistically, the distribution of cortical interneurons was disrupted. The distribution of interneuron subtypes was abnormal both in the cortex and hippocampus after the VPA exposure, which affected the somatostatin-positive neurons but not the parvalbumin-positive neurons, indicating the effects of VPA were subtype specific. Biological processes related to ion homeostasis were greatly changed after VPA exposure.
conclusionPrenatal VPA exposure during the neurogenic period impaired the cognition of the offspring by disrupting interneuron migration and differentiation. The study provides a novel perspective on the influence of VPA over neurodevelopment.
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