Effects and mechanisms of vitamins A and D on behavior associated with Tourette syndrome in rats.

Background and aims: Tourette syndrome (TS) is a complex neurodevelopmental disorder involving genetic, neurotransmission, immune, and gut-brain axis mechanisms that cause persistent motor and vocal tics. Current treatments mainly include drugs (for example, neuroleptics), but the treatment strategies are often unsatisfactory. Retinoic acid, derived from vitamin A, plays a role in TS, as children with this condition often exhibit reduced serum levels of retinoic acid and 25-hydroxyvitamin D. Supplementing with either nutrient has been shown to alleviate tic severity and frequency. In this study, we aim to explore the therapeutic effects and possible mechanisms of vitamins A and D in TS. Methods: 3,3-Iminodipropionitrile (IDPN) was used to induce acute TS-like symptoms in rats via striatal dopamine dysregulation. Then vitamins A (3 mg/kg/d) and D (10ug/kg/d) were continuously administered by gavage for 8 weeks. Stereotyped and head twitching behavior tests were then performed. High-performance liquid chromatography was used to determine serum levels of 25-OH-D3, calcium, phosphorus, and alkaline phosphatase in rats. The composition of intestinal flora was analyzed using 16S rRNA gene sequencing, and striatum metabolites were detected by untargeted metabolomics. Results: The experimental results showed that the tic phenotype of TS rats was significantly relieved after 8 weeks of vitamin A and D treatment ( Conclusion: This study shows that vitamin A and D supplementation can significantly alleviate the tic phenotype of TS rats, which demonstrates an association between vitamin A/D-induced gut flora alterations and neurotransmitter changes. Further research is needed to establish direct causal relationships in the gut-brain axis pathway.