Summary: | 碩士 === 國立陽明大學 === 解剖暨細胞生物學研究所 === 95 === Backgrouds: Antidepressants are the main treatments for depression. Several studies have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and BDNF signaling is important for the therapeutic mechanism of antidepressants. Recent work has found that cysteamine and its dimmer, cystamine, are neuroprotective in Huntington’s disease (HD) mice by enhancing the secretion of central BDNF. Furthermore, cysteamine or cystamine injection could increase serum BDNF levels. In this study, the potential antidepressant effects of cysteamine were examined by behavioral paradigms and biochemical assay. Methods: Male BALB/CByJ mice (age 7-9 weeks) were used in this study. Each mouse was given a single dose of normal saline, imipramine (10mg/kg) or 50, 100 or 200mg/kg of cysteamine by i.p. route 30min before the forced swimming test (FST) or the tail suspension test (TST). BDNF levels after drug treatment were also examined by ELISA. Comparisons among treatments groups were performed by one-way analysis of variance followed by Scheffe’s post-hoc test. A p value <0.05 was considered to be significant in another five groups of mice with same treatment. Results: Compared with the control group, the cysteamine 200mg/kg group showed a significant increase in struggling time in the TST (p < 0.01, n=19-20/group) and, a trend of increasing in struggling time in the FST was also observed (p=0.164, n=5/group), while the locomotor activity by the open field test in this group was reduced (p < 0.01, n=7/group). A significant increase in hippocampal BDNF levels was found in the cysteamine 200mg/kg group (p < 0.05, n=13-14/group). Conclusions: After acute drug treatment, cysteamine demonstrated antidepressant-like effects in the TST and FST, and also increases the BDNF levels in hippocampus. These results suggest that cysteamine may posess antidepressant-like effect, which may be mediated by increasing central BDNF levels.
Key words: antidepressants, hippocampus, brain-derived neurotrophic factor, cysteamine, open field test, forced swimming test, tail suspension test, ELISA
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