| Summary: | 碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 100 === Background: Depression is a psychiatric disorder characterized by depressed mood, hopelessness, helplessness, and loss of interest. It has been known that stress may inhibit neurogenesis and decrease brain-derived neurotrophic factor (BDNF) levels, while exercise can increase neurogenesis and BDNF levels in rodents. In order to clarify the role of exercise in depression, we used an animal model of depression and spontaneous wheel running to study the effects of exercise on stress-induced helpless behavior, neurogenesis, and BDNF levels in the hippocampus of mice.
Materials and methods: Nine weeks old male C57BL/6J Narl mice were screened with the escape test and only those with a ≤ 30% failure rate were used in this study. The mice were given inescapable footshock stress (100 V, 0.6 mA, 4s every 3-5 min, 6hrs/day) for three consecutive days and then assessed with the escape test. A mouse with a > 70% failure rate after the stress was regarded as helpless. Helpless mice were randomly assigned to the wheel (n= 22) and no-wheel (n= 25) groups. Each mouse was kept in an individual cage. Running wheel activity was measured by automatically counting the number of revolutions per hour during the experiment. All the mice were re-assessed with the escape test on the 14th and 28th day after becoming helpless and then sacrificed on the 29th day. The right hippocampus was preserved for immunohistochemical staining with DCX and the left hippocampus was homogenized for BDNF ELISA measurement. A group of mice without inescapable footshock stress were used in the DCX and BDNF study. SPSS statistical software was used for statistical analysis.
Results: The failure rate in the escape test for the wheel group (14th day: 53.1± 6.6%, 28th day: 48.2± 8.6%) was significantly lower than the no-wheel group (14th day: 85.4± 4.4%, 28th day: 86.6± 4.4%) (p≤ 0.01), but the failure rate was not significantly different between the 14th day and 28th day’s assessments (p= 0.34). Pearson correlation coefficient analysis revealed a negative correlation between the wheel-running distance (r=-0.517, p≤ 0.01) and the escape failure rate (r=-0.536, p≤ 0.01), however, the correlation (r=-0.434, p= 0.16) disappeared when the wheel-running distance was longer than 160 km. DCX-staining area in the dentate gyrus of the helpless mice was smaller than the mice without inescapable stress (p≤ 0.01). DCX-staining area in the dentate gyrus of the wheel group was larger than that of the no-wheel group (p≤ 0.01), but smaller than the mice without stress (p≤ 0.01). There was a positive correlation between wheel running distance and DCX area when the distance was below 160km (r= 0.746, p≤ 0.05), but the correlation became negative when the distance was longer than 160 km (r= -0.812, p≤ 0.01). Neither inescapable footshock stress nor wheel running resulted in significant alteration in hippocampal BDNF concentration (F(2, 39)= 0.56, p= 0.58).
Conclusion: Inescapable footshock stress induced helpless (depression-liked) behavior and reduced neurogenesis in the dentate gyrus of mice could be improved by spontaneous wheel-running exercise. However, long-term spontaneous exercise effects have upper limit for helpless (depression-liked) behavior and neurogenesis. Our results indicate that moderate level of exercise could be helpful in treating depression.
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