Antidepressant-like effects of fenofibrate in mice via the hippocampal brain-derived neurotrophic factor signalling pathway
Antidepressant-like effects of fenofibrate in mice via the hippocampal brain-derived neurotrophic factor signalling pathway
复制标题
非诺贝特通过海马脑源性神经营养因子信号通路对小鼠产生抗抑郁样作用
DOI：
10.1111/bph.13668
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发表时间：
2017-01-01
影响因子：
7.3
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Jiang, Bo;Wang, Ying-Jie;Zhang, Wei
背景和目的抑制是一种神经精神疾病，伴随着脑衍生的神经营养因子（BDNF）信号级联的降低。 fenofibrate是PPAR-Alpha的选择性激动剂。在这项研究中，我们研究了Fenobinate在C57BL/6J小鼠中的抗抑郁样作用。实验方法在强制游泳试验（FST）和尾悬架测试（TST）（TST）中首先鉴定出抗抑郁剂的抗抑郁样作用，然后在慢性社会失败应力（CSDS）模型中进行评估。进一步研究了海马BDNF信号通路和成年海马神经发生后CSD和非诺贝特治疗后的变化。 PPAR-α抑制剂，大麻素系统抑制剂和BDNF信号传导抑制剂也被用于确定非诺贝特的抗抑郁机制。基诺型纤维纤维型施用在FST和TST中表现出抗抑郁药样效应，而不会影响小鼠的运动能力活性。慢性非诺贝特治疗还防止了CSD诱导的抑郁样症状。此外，非诺贝特恢复了CSDS诱导的海马BDNF信号级联和成年海马神经发生的降低。 fenobrate的抗抑郁样作用可以通过PPAR-Alpha抑制剂和BDNF信号抑制剂来阻止。核心和含义剂在一起，这些结果表明，fenofibrate具有抗抑郁剂的抗抑郁样效应，通过促进Hippocampal bdnf信号仪的抗抑郁样效应。
BACKGROUND AND PURPOSEDepression is a neuropsychiatric disorder accompanied by a decrease in the brain-derived neurotrophic factor (BDNF) signalling cascade in the hippocampus. Fenofibrate is a selective agonist of PPAR-alpha. In this study, we investigated the antidepressant-like effects of fenofibrate in C57BL/6J mice.EXPERIMENTAL APPROACHThe antidepressant-like effects of fenofibrate were first identified in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model. The changes in the hippocampal BDNF signalling pathway and adult hippocampal neurogenesis after CSDS and fenofibrate treatment were further investigated. A PPAR-alpha inhibitor, cannabinoid system inhibitors and BDNF signalling inhibitors were also used to determine the antidepressant mechanisms of fenofibrate.KEY RESULTSFenofibrate administration exhibited antidepressant-like effects in the FST and TST without affecting the locomotor activity of mice. Chronic fenofibrate treatment also prevented the depressive-like symptoms induced by CSDS. Moreover, fenofibrate restored the CSDS-induced decrease in the hippocampal BDNF signalling cascade and adult hippocampal neurogenesis. The antidepressant-like effects of fenofibrate could be blocked by a PPAR-alpha inhibitor and BDNF signalling inhibitors.CONCLUSIONS AND IMPLICATIONSTaken together, these results suggest that fenofibrate has antidepressant-like effects mediated through the promotion of the hippocampal BDNF signalling cascade.