Hippocampal BDNF signaling restored with chronic asiaticoside treatment in depression-like mice
Hippocampal BDNF signaling restored with chronic asiaticoside treatment in depression-like mice
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DOI：
10.1016/j.brainresbull.2015.03.006
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发表时间：
2015-05-01
影响因子：
3.8
通讯作者：
Yi, Li-Tao
中科院分区：
文献类型：
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作者：
Luo, Liu;Liu, Xiao-Long;Yi, Li-Tao
脑源性神经营养因子(BDNF)在脑内抑郁的调节中起着关键作用。近年来，越来越多的研究集中于BDNF的抗抑郁作用机制及其下游信号通路。此前的一项研究表明，积雪草苷在小鼠尾部悬吊实验和强迫游泳实验中具有抗抑郁作用。然而，积雪草苷影响神经营养的机制尚不清楚。本研究旨在验证积雪草苷是否通过激活脑源性神经营养因子信号通路在慢性不可预测的轻度应激(CUMS)中产生抗抑郁药样作用。结果表明，积雪草苷治疗四周后，能逆转CUMS小鼠降低的蔗糖偏好和延长的不动时间。此外，我们发现积雪草苷上调BDNF、PSD-95和突触素I的表达仅在非应激和CUMS小鼠的海马区，而在额叶皮质不表达。然而，BDNF受体原肌球蛋白相关激酶受体B(TrkB)的抑制剂K252a完全取消积雪草苷的抗抑郁药样作用。此外，随着积雪草苷的增加，海马区BDNF、PSD-95和突触素I的表达也随着K252a的处理而降低。综上所述，我们的研究表明积雪草苷可能通过激活海马区的BDNF信号来发挥其抗抑郁药样作用。(C)2015 Elsevier Inc.保留所有权利。
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. (C) 2015 Elsevier Inc. All rights reserved.