Physical Exercise Prevents Mouse from KYN-induced Depression-like Behavior

• Main Authors: Cheng-Hua Su, 蘇政華
• Other Authors: Chen-Jee Hong
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/2z655d

碩士 === 國立陽明大學 === 腦科學研究所 === 105 === Background: Several studies have suggested that physical exercise can relieve depressed mood. Our previous study also found that running wheels reduced stress-induced depression-like behavior in mice. Some studies indicated that increased plasma kynurenine (KYN) level was related to depressive symptoms. In 2014, Agudelo et al. reported that exercise relieved stress-induced depression by enhancing KYN metabolism. This study seeks to test the effect of exercise on KYN-related depressive behavior in mice. Hypothesis: Exercise prevents depressive behavior induced by KYN. Methods: Mice in exercise group were individually raised in cages with a wheel that was freely accessible. Mice in control group were individually kept in cages without a wheel. After 3 weeks, the mice were given an injection of either 20mg/kg KYN or equal volume of saline 30 min before the tail-suspension test (TST). The escape test was conducted one week later. At the fifth week, both control and exercised mice were divided to KYN and control groups, then sacrificed 30 min after an injection of KYN (20mg/kg) or saline, respectively. Whole blood was collected for plasma KYN measurement using ELISA. Total RNA was extracted from the hind leg soleus. KYN- metabolizing enzyme kynurenine aminotransferase 3 (KAT3) was quantitated using qPCR. Results: Exercised mice’s plasma KYN concentration (3.29±1.09uM) was as low as a quarter of that of control (12.95±3.44uM) (P<0.01). Normal mice injected with KYN showed increased immobile time in the TST (214±30s for KYN vs. 181±33s 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. Finally, we found exercised mice expressed more KAT3 in the soleus 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 KYN-induced depressive behavior.