Assessment of Cholecalciferol's Therapeutic Efficacy on the Cerebellum in an Autistic Male Pup Model

Background: Autism spectrum disorder (ASD), neurodevelopmental disorder, is found to be linked to pathological changes in the cerebellum. Interestingly, vitamin D is reported to be deficient in autistic kids. Objective: This study aimed to demonstrate the effect of cholecalciferol administration on impaired autophagy in the cerebellum of male rat pups in a postnatal valproate (VPA)-induced model of autism. Materials and methods: A total of 15 Sprague-Dawley male rat pups were used to assess the possible therapeutic effects of vitamin D (cholecalciferol) on the cerebellum of autistic rats through autophagy augmentation. The rats were divided equally into three groups. The control group received saline on the 14th postnatal day, while valproate (VPA) group received single dose of 400-mg/kg VPA on same day. The cholecalciferol-treated group received a single dose of VPA on the 14th postnatal day followed by a single intramuscular injection of cholecalciferol on the 21st postnatal day. At the assigned time, the animals were sacrificed, and cerebellar tissue samples were taken for biochemical, histological, and immunohistochemical analyses. Results: VPA treatment increased the oxidative stress marker malondialdehyde (MDA) significantly. Histological examination revealed disrupted cerebellar architecture and the light chain3-II (LC3-II) immunohistochemical expression dropped significantly in VPA group. Co-treatment with cholecalciferol significantly reversed the previous changes. Conclusion: Cholecalciferol has neuroprotective activity on the cerebellum of autistic rats due to its antioxidant mechanisms as well as its ability to improve autophagy.