MiR-134 modulates chronic stress-induced structural plasticity and depression-like behaviors via downregulation of Limk1/cofilin signaling in rats
MiR-134 modulates chronic stress-induced structural plasticity and depression-like behaviors via downregulation of Limk1/cofilin signaling in rats
复制标题
MiR-134 通过下调大鼠 Limk1/cofilin 信号传导来调节慢性应激诱导的结构可塑性和抑郁样行为。
DOI：
10.1016/j.neuropharm.2018.01.009
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发表时间：
2018-03-15
影响因子：
4.7
通讯作者：
Yu, Shu Yan
中科院分区：
文献类型：
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作者：
Fan, Cuiqin;Zhu, Xiuzhi;Yu, Shu Yan
越来越多的证据表明，抑郁症是一种与特定脑区的神经可塑性相关的神经精神疾病。然而，神经可塑性在抑郁症中发挥作用的机制在很大程度上仍然没有得到表征。在本研究中，我们表明，慢性应激有效地诱导抑郁样行为的大鼠，这是与树突棘和腹内侧前额叶皮层（vmPFC）神经元内的突触异常的结构变化的影响。此外，不可预测的慢性轻度应激（UCMS）暴露显著增加了vmPFC内miR-134的表达，这一效应与突触相关蛋白LIM结构域激酶1（Limk 1）和cofilin的表达和磷酸化水平降低相一致。将腺病毒相关病毒（AAV）-miR-134-海绵体脑内输注到应激大鼠的vmPFC中，其阻断mir-134功能，显著改善神经元结构异常、生化变化和抑郁样行为。慢性给药的人参皂苷Rg 1（40 mg/kg，5周），一个潜在的神经保护剂，从人参中提取，显着改善UCMS暴露引起的行为和生化变化。这些结果表明，miR-134介导的结构可塑性失调可能与应激大鼠抑郁样行为的表现有关。在这种抑郁模型中产生抗抑郁样作用的miR-134 Rg 1的神经保护作用似乎是由vmPFC内miR-134信号通路的调节引起的。(C)2018爱思唯尔有限公司版权所有
Increasing evidence has suggested that depression is a neuropsychiatric condition associated with neuroplasticity within specific brain regions. However, the mechanisms by which neuroplasticity exerts its effects in depression remain largely uncharacterized. In the present study we show that chronic stress effectively induces depression-like behaviors in rats, an effect which was associated with structural changes in dendritic spines and synapse abnormalities within neurons of the ventromedial prefrontal cortex (vmPFC). Moreover, unpredictable chronic mild stress (UCMS) exposure significantly increased the expression of miR-134 within the vmPFC, an effect which was paralleled with a decrease in the levels of expression and phosphorylation of the synapse-associated proteins, LIM-domain kinase 1 (Limk1) and cofilin. An intracerebral infusion of the adenovirus associated virus (AAV)-miR-134-sponge into the vmPFC of stressed rats, which blocks mir-134 function, significantly ameliorated neuronal structural abnormalities, biochemical changes and depression-like behaviors. Chronic administration of ginsenoside Rg1 (40 mg/kg, 5 weeks), a potential neuroprotective agent extracted from ginseng, significantly ameliorated the behavioral and biochemical changes induced by UCMS exposure. These results suggest that miR-134-mediated dysregulation of structural plasticity may be related to the display of depression like behaviors in stressed rats. The neuroprotective effects of ginsenoside Rg1, which produces an antidepressant like effect in this model of depression, appears to result from modulation of the miR-134 signaling pathway within the vmPFC. (C) 2018 Elsevier Ltd. All rights reserved.