LAUSR

BACKGROUND Depression is a wide-spread disease that affects millions of people worldwide. Recent studies in neuroinflammation suggested that increased plasma kynurenine (KYN) level was related to depressive symptoms, while animal studies indicated that KYN increase could be caused by environmental stressor. Recent study reported that exercise may prevent stress-induced depression by enhancing KYN metabolism in muscle. This study seeks to test the effect of voluntary exercise on depressive-like behavior induced by stress and KYN in mice. HYPOTHESIS Exercise prevents depressive-like behavior induced by KYN. RESULTS Our study found that two weeks of voluntary exercise greatly reduced stress-induced helplessness in mice. On non-stressed mice, naïve mice injected with KYN showed increased immobile time in the TST (214 ± 30 s for KYN vs. 181 ± 33 s for saline; p < 0.05) and higher failure rate in the escape test (39 ± 31 % for KYN vs. 16 ± 13 % for saline; p < 0.05), while exercised mice were not affected by KYN injection in neither test. We also observed that exercised mice's plasma KYN concentration (3.29 ± 1.09 u M) was as low as a quarter of that of control (12.95 ± 3.44 u M) (P < 0.01) after KYN injection. Finally, we found that exercised mice expressed more kynurenine aminotransferase III (KAT3) in the muscle than control mice (1.62 ± 0.60 folds for exercise vs. 1.00 ± 0.22 folds for control; p = 0.005) CONCLUSION: Exercise promotes KAT3 expression, enhances KYN metabolism, and consequently prevents mice from stress or KYN-induced depressive-like behavior.