Abstract
The prevalence of autism spectrum disorder (ASD) has been increasing, with recent estimates suggesting that 2.7% of children in the U.S. are diagnosed with ASD. Among environmental risk factors, prenatal exposure to valproic acid (VPA), an antiepileptic drug, has been shown to increase ASD risk. This review provides an integrative discussion of the association between VPA exposure and ASD, focusing on developmental neurotoxicity mechanisms and animal models. VPA's neurotoxicity affects epigenetic modifications, neural stem cell proliferation and differentiation, synaptogenesis, and neurotransmitter systems. These changes may underlie behavioral abnormalities and neurological features observed in ASD. Animal models exposed to VPA exhibit ASD-like behaviors and neurological changes, contributing to our understanding of ASD pathomechanisms. While environmental factors like VPA contribute to only a fraction of ASD cases, their study is crucial for identifying preventable risk factors. Future research should elucidate genetic-environmental interactions, advance epigenetics research, analyze time- and dose-dependent effects of environmental factors, integrate findings from animal models with human studies, apply findings to personalized medicine, and develop novel therapies. These efforts aim to enhance our understanding of ASD's complex pathomechanisms, potentially leading to effective prevention and treatment methods.
