Maternal arsenic exposure induces autism-like behaviors via astrocyte-mediated neuronal apoptosis: Protective effects of Taurine.

Abstract

Autism spectrum disorder (ASD) is associated with reduced serum taurine (TA) levels in children with ASD. However, the protective effects of TA against As-associated neurodevelopmental injury remain unclear. Here, we investigated whether TA ameliorates maternal As exposure-associated ASD-like behaviors and explored the underlying mechanisms. Pregnant Sprague-Dawley rats received As₂O₃ and TA through drinking water during gestation. Offspring behaviors and prefrontal cortical changes were assessed using behavioral, histological, ultrastructural, biochemical, and cell-based assays. Maternal As exposure impaired social preference and social novelty preference and increased repetitive, stereotyped, and anxiety-like behaviors, whereas TA treatment ameliorated these abnormalities. In the prefrontal cortex, As exposure increased synaptic cleft width by 39.80%, reduced postsynaptic density thickness by 17.28%, and increased Cleaved Caspase-3 expression to 3.38-fold that of the CTL group. The density of TUNEL⁺/NeuN⁺ cells increased from 38.10 to 213.34 cells/mm², whereas TA treatment reduced it to 42.45 and 40.27 cells/mm², respectively. TA also attenuated astrocyte hyperactivation and A1-like phenotypic alteration, restored the NGF/TrkA pathway, and reduced astrocyte-mediated neuronal apoptosis in vitro. TrkA inhibition weakened the anti-apoptotic effect of TA. These findings suggest that TA may alleviate As-associated neurodevelopmental injury by modulating astrocyte reactivity and promoting neuronal survival.