Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province, 250012, PR China.
Department of Physiology, Shandong University, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province, 250012, PR China; Shandong Provincial Key Laboratory of Mental Disorders, School of Medicine, Wenhuaxilu Road, Jinan, Shandong Province, 250012, PR China.
Neuropharmacology. 2018 Mar 15;131:364-376. doi: 10.1016/j.neuropharm.2018.01.009. Epub 2018 Jan 9.
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.
越来越多的证据表明，抑郁症是一种与特定脑区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未得到阐明。在本研究中，我们表明慢性应激能有效地在大鼠中诱导出类似抑郁的行为，这种效应与腹内侧前额叶皮质（vmPFC）神经元中树突棘和突触的结构变化有关。此外，不可预测的慢性轻度应激（UCMS）暴露显著增加了 vmPFC 中 miR-134 的表达，这种效应与突触相关蛋白 LIM 激酶 1（Limk1）和丝切蛋白的表达和磷酸化水平降低相平行。将腺相关病毒（AAV）-miR-134-海绵体注入应激大鼠的 vmPFC 中，阻断 miR-134 的功能，可显著改善神经元结构异常、生化变化和类似抑郁的行为。人参中提取的潜在神经保护剂人参皂苷 Rg1（40mg/kg，5 周）的慢性给药，可显著改善 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表现出类似抑郁的行为有关。人参皂苷 Rg1 产生抗抑郁样作用的神经保护作用似乎是通过调节 vmPFC 中的 miR-134 信号通路实现的。
