Creatine differently prevents chronic colitis-induced motor deficits, anxiety and depressive behaviors, neuroinflammation, and microglial activation in male and female rats

Abstract

Creatine has been reported to exhibit neuroprotective and anti-inflammatory properties and alleviate symptoms of affective disorders. In this study, we used a chronic colitis model in male and female rats, using a dextran sulfate sodium treatment that mimics the remitting–relapsing phases of human ulcerative colitis. The results showed that in rats with colitis, oral creatine supplementation reduced the severity of colitis symptoms and prevented motor deficits, anxiety, and depression-like behaviors. These effects of creatine were consistent throughout the development of chronic colitis, remaining independent of remitting–relapsing periods. In response to creatine supplementation, colon and brain creatine levels increased in rats with chronic colitis without sex differences. Furthermore, at the end of the treatment, when chronic colitis was established, creatine ameliorated injury of colonic surface epithelial and prevented chronic colitis-associated neuroinflammation, evidenced by a decrease in the pro-inflammatory cytokines IL-1β, IL-6, and TNF mRNA, as well as microglial activation in the prefrontal and motor cortices of rats of both sexes. In general, creatine supplementation was more effective in females. In conclusion, creatine supplementation had sex-specific effects and could serve as a nutritional strategy to reduce the severity of colitis and its associated motor and mood disturbances, neuroinflammation, and microglial activation.