Prenatal valproic acid exposure alters striatal proteomic signatures associated with autism spectrum disorder in mice - PubMed
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- #autism spectrum disorder
- #prenatal exposure
- #proteomics
- Prenatal valproic acid (VPA) exposure is a known environmental risk factor for autism spectrum disorder (ASD).
- Proteomic analysis of the striatum in VPA-exposed mice revealed 101 differentially expressed proteins (47 upregulated, 54 downregulated).
- Key downregulated proteins include parvalbumin (PVALB), NR2F1, and metallothioneins (MT1, MT2, MT3), affecting inhibitory signaling and redox regulation.
- Functional pathways implicated include synaptic transmission, neuronal development, metal ion homeostasis, oxidative stress response, and E/I balance.
- PVALB and MT2 were identified as hub proteins in protein-protein interaction networks, linking synaptic, glial, and oxidative stress modules.
- Histological validation showed reduced PVALB immunoreactivity in the dorsolateral striatum, with a trend in the dorsomedial striatum.
- Behavioral assessment confirmed ASD-like phenotypes, such as reduced body/brain weights and increased repetitive self-grooming in VPA-exposed mice.