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Neurotrophic factors are well-known to be involved in the pathophysiology of depression and treatment of antidepressants. Brain-derived neurotrophic factor (BDNF), one of the most widely distributed and the most highly studied neurotrophic factors, has been demonstrated to play an important role in the pathophysiology of depression and the mechanism of antidepressants. According to the previous studies, we found that animal tissues were dissected for BDNF measurement mainly in daytime. Considering the circadian rhythm of BDNF expression, our present study evaluated the circadian variations in behaviors, serum corticosterone concentrations, hippocampal BDNF expression and neuronal cell proliferation in mice exposed to chronic mild stress (CMS), one of the most widely used depression-like animal models. Our results provided the first evidence that the difference of BDNF expression and neuronal cell proliferation between CMS and control mice underwent an oscillation related to the circadian variations (maximum at 20:00 h, minimum at 12:00 h or 16:00 h), while the difference of sucrose preference and first feeding latency was not affected by circadian rhythm. This oscillation difference was attributed to the relative constant BDNF expression and cell proliferation in CMS mice and the fluctuating BDNF expression and cell proliferation in control mice. CMS exposure might destroy the circadian rhythm of BDNF expression and cell proliferation in hippocampus of normal individual. Our present study suggests that animal decapitation at 20:00 h is the best time for BDNF-related measurement in CMS experiment, since the difference reaches the maximum.

Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of depression in the brain. Recently, increasing studies have focused on the antidepressant-like mechanism of BDNF and its downstream signaling pathway. A previous study has shown that asiaticoside produced an antidepressant-like action in the mouse tail suspension test and forced swimming test. However, the neurotrophic mechanism that is affected by asiaticoside is unclear. Our present study aimed to verify whether asiaticoside produces an antidepressant-like effect through the activation of BDNF signaling in chronic unpredictable mild stress (CUMS). The results showed that mice treated with asiaticoside for four weeks reversed the decreased sucrose preference and increased immobility time that was observed in CUMS mice. In addition, we found that asiaticoside up-regulated BDNF, PSD-95 and synapsin I expression only in the hippocampus but not in the frontal cortex in both non-stressed and CUMS mice. However, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), completely abolished the antidepressant-like effect of asiaticoside. Moreover, the expression of hippocampal BDNF, PSD-95 and synapsin I that had increased with asiaticoside also declined with K252a pretreatment. In conclusion, our study implies that it is possible that asiaticoside exerts its antidepressant-like action by activating BDNF signaling in the hippocampus. [ABSTRACT FROM AUTHOR]