Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF
Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF
复制标题
海马miR-206-3p通过调节BDNF表达参与抑郁症发病机制
DOI：
10.1016/j.phrs.2021.105932
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发表时间：
2021-10-21
影响因子：
9.3
通讯作者：
Jiang, Bo
中科院分区：
文献类型：
--
作者：
Guan, Wei;Xu, Da-Wei;Jiang, Bo
抑郁症是一种广泛存在的神经精神疾病，其确切的发病机制尚不清楚。miRNA-206（miR-206）通常被称为myomiR之一，并且具有两种形式：miR-206- 3 p和miR-206- 5 p。最近，miR-206已被证明可以调节脑源性神经营养因子（BDNF）的生物合成，BDNF是一个非常受欢迎的参与抑郁症和抗抑郁反应的靶点。本研究假设miR 206可能在抑郁症中发挥作用，综合运用慢性社会失败应激（CSDS）抑郁症模型、实时定量逆转录PCR、免疫荧光、Western blotting、病毒介导的基因转移等多种方法，对miR 206在抑郁症中的作用进行了研究。发现CSDS稳健地增加海马中miR-206- 3 p的水平，但不增加miR-206- 5 p的水平。海马miR-206- 3 p的基因过表达和AgomiR-206- 3 p的鼻内给药不仅诱导了明显的抑郁样行为，而且显著降低了幼稚C57 BL/6 J小鼠海马BDNF信号级联和神经发生。相比之下，海马miR-206- 3 p的基因敲低和AntagomiR-206- 3 p的鼻内给药在抑郁症的CSDS模型中产生显著的抗抑郁样作用。此外，发现由miR-206- 3 p抑制诱导的抗抑郁样作用需要海马BDNF-TrkB系统。综上所述，海马miR-206- 3 p通过调节BDNF的生物合成参与抑郁症的发病机制，是一个可行的抗抑郁靶点。
As a widely-known neuropsychiatric disorder, the exact pathogenesis of depression remains elusive. MiRNA-206 (miR-206) is conventionally known as one of the myomiRs and has two forms: miR-206-3p and miR-206-5p. Recently, miR-206 has been demonstrated to regulate the biosynthesis of brain-derived neurotrophic factor (BDNF), a very popular target involved in depression and antidepressant responses. Here we assumed that miR206 may play a role in depression, and various methods including the chronic social defeat stress (CSDS) model of depression, quantitative real-time reverse transcription PCR, western blotting, immuofluorescence and virusmediated gene transfer were used together. It was found that CSDS robustly increased the level of miR-206-3p but not miR-206-5p in the hippocampus. Both genetic overexpression of hippocampal miR-206-3p and intranasal administration of AgomiR-206-3p induced not only notable depressive-like behaviors but also significantly decreased hippocampal BDNF signaling cascade and neurogenesis in naive C57BL/6J mice. In contrast, both genetic knockdown of hippocampal miR-206-3p and intranasal administration of AntagomiR-206-3p produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, it was found that the antidepressant-like effects induced by miR-206-3p inhibition require the hippocampal BDNF-TrkB system. Taken together, hippocampal miR-206-3p participates in the pathogenesis of depression by regulating BDNF biosynthesis and is a feasible antidepressant target.