Vitamin A supplementation restores neuroanatomical integrity and behavior in a valproic acid-induced autism model.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviors, and cognitive impairments. Evidence suggests that Vitamin A deficiency (VAD) may exacerbate ASD-related abnormalities, while Vitamin A supplementation (VAS) may offer neuroprotection. This study investigates the effects of Vitamin A modulation on neuronal integrity, cognitive function, and social behavior in a valproic acid (VPA)-induced ASD rat model, focusing on histological changes, behavioral outcomes, and serum Vitamin A levels. Pregnant Wistar rats received VPA (500 mg/kg) on gestational day 12.5. Offspring were divided into Control, VPA, VAD, VPA + VAD, and VPA + VAS (2000 IU/kg diet) groups. Serum Vitamin A levels were quantified using spectrophotometry. Histopathological analysis of the hippocampus, cerebellum, and prefrontal cortex (PFC) assessed neuronal and glial cell densities. Behavioral tests included the Three-Chamber Social Interaction Test for sociability and the Novel Object Recognition Test for memory function. Serum analysis showed significantly lower Vitamin A levels in VAD and VPA + VAD groups, while VAS restored levels. Histological analysis revealed reduced neuronal density and increased glial activation in VPA, VAD, and VPA + VAD groups. The VPA + VAS group exhibited partial neuronal recovery. Behaviorally, VAS improved sociability and memory performance, correlating with neuronal preservation. These findings suggest that Vitamin A deficiency worsens ASD-related impairments, while supplementation restores neuronal integrity and cognitive function, highlighting its potential therapeutic role in ASD.