Voluntary wheel running from early adolescence reduces disease progression, and anxiety- and depression-related symptoms in an adult male mouse model of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that progressively destroys synovial joints and leads to chronic systemic inflammation. This autoimmune disorder is associated with increased anxiety- and depression-related symptoms, which reduces quality of life. Clinical and experimental evidence suggests that higher physical activity from early adolescence may prevent chronic diseases and reduce the risk of mental health problems in adulthood. This study aimed to assess whether voluntary wheel running from early adolescence can decrease clinical symptoms, anxiety- and depression-related behaviors in adult mice with rheumatoid arthritis. Adolescent male mice were exposed to voluntary wheel running until adulthood and got collagen-induced arthritis. We measured body weight, the thickness of the hind paw and knee joint (clinical signs), anxiety- and depression-related behaviors, serum testosterone, and cytokines (IFN-γ IL-1β, IL-6, TNF-α, IL-10). The findings showed that collagen-induced arthritis resulted in anxious-like behavior, increased anhedonia, elevated IL-6, IL-1β, TNF-α, and IFN-γ, and decreased testosterone levels in the serum of mice. However, no change was observed in behavioral despair. We found that higher physical activity from early adolescence significantly reduced the severity of clinical signs, anxiety- and anhedonia-like behaviors, and decreased behavioral despair in RA-induced mice. In addition, the running wheel exposure normalized RA-induced abnormalities in testosterone and inflammatory cytokines in mice. Altogether, this study suggests that higher physical activity from early adolescence may make mice less vulnerable or resistant to RA-induced clinical symptoms and anxiety- and depression-related behaviors by changing testosterone and inflammatory cytokines productions in adulthood.