VITAMIN A STATUS MODULATES NEURODEVELOPMENTAL, OXIDATIVE, AND CHOLINERGIC ALTERATIONS IN A VALPROIC ACID–INDUCED RAT MODEL OF AUTISM

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition in which early environmental and nutritional factors critically influence brain maturation. Vitamin A plays essential roles in neuronal differentiation, redox regulation, and cholinergic neurotransmission; however, its contribution to ASD-related neurobiological alterations remains insufficiently characterized. We investigated the effects of maternal vitamin A deficiency and supplementation on neurodevelopmental behavior, oxidative stress, and cholinergic function using a valproic acid (VPA)–induced rat model of autism. Twenty-five pregnant Wistar rats were allocated into five groups: control, VPA-exposed, vitamin A–deficient (VAD), combined VPA and vitamin A deficiency (VPA+VAD), and VPA with vitamin A supplementation (VPA+VAS). VPA was administered during gestation, while vitamin A status was modulated through dietary intervention from pregnancy to lactation. Offspring underwent neurodevelopmental and behavioral assessments, followed by biochemical analyses of oxidative stress markers and cholinergic parameters, as well as histological evaluation of selected brain regions. VPA exposure induced significant behavioral impairments compared with controls (p < 0.01), which were exacerbated by vitamin A deficiency. Offspring from the VPA+VAD group showed increased lipid peroxidation (p < 0.001) and reduced antioxidant defenses (p < 0.01), accompanied by disrupted cholinergic homeostasis, including elevated acetylcholinesterase activity (p < 0.01). In contrast, vitamin A supplementation improved behavioral performance (p < 0.05) and partially restored oxidative and cholinergic balance compared with the VPA group (p < 0.05). These findings demonstrate that vitamin A status modulates neurodevelopmental vulnerability in a VPA-induced ASD model, supporting vitamin A as a preventive target.