HuR in the Medial Prefrontal Cortex is Critical for Stress-Induced Synaptic Dysfunction and Depressive-Like Symptoms in Mice
HuR in the Medial Prefrontal Cortex is Critical for Stress-Induced Synaptic Dysfunction and Depressive-Like Symptoms in Mice
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内侧前额叶皮质中的 HuR 对于小鼠压力引起的突触功能障碍和抑郁样症状至关重要
DOI：
10.1093/cercor/bhz036
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发表时间：
2019-06-01
期刊：
影响因子：
3.7
通讯作者：
Zhu, Xiao-Juan
中科院分区：
文献类型：
--
作者：
He, Zi-Xuan;Song, Hui-Fang;Zhu, Xiao-Juan
慢性应激已被观察到增加患抑郁症的风险并诱导突触可塑性的神经元改变，但其潜在的分子机制尚不清楚。在这里，我们发现在慢性应激小鼠的内侧前额叶皮层（mPFC）中普遍表达的rna结合蛋白HuR上调。在成年小鼠中，aav - cre介导的mPFC中HuR的敲除可以防止慢性应激诱导的焦虑样和抑郁样行为。应激诱导的树突棘丢失和突触传递缺陷也需要HuR。此外,户珥(液氧/液氧);从胚胎发育开始诱导HuR功能丧失的Nex-Cre小鼠表现出增强的突触功能。值得注意的是，我们确定了RhoA信号是由HuR调节的，并参与了慢性应激下突触结构可塑性的调节。我们的研究结果表明，HuR是调节应激诱导的突触可塑性改变和抑郁的关键调节剂，为抑郁症的治疗提供了潜在的治疗靶点。
Chronic stress has been observed to increase the risk of developing depression and induce neuronal alterations of synaptic plasticity, yet the underlying molecular mechanisms remain unclear. Here, we found that the ubiquitously expressed RNA-binding protein HuR was up-regulated in the medial prefrontal cortex (mPFC) of mice following chronic stress. In adult mice, AAV-Cre-mediated knockout of HuR in the mPFC prevented anxiety-like and depression-like behaviors induced by chronic stress. HuR was also required for the stress-induced dendritic spine loss and synaptic transmission deficits. Moreover, HuR(flox/flox); Nex-Cre mice, which induce HuR loss of function from embryonic development, exhibited enhanced synaptic functions. Notably, we ascertained RhoA signaling to be regulated by HuR and involved in the modulation of structural synaptic plasticity in response to chronic stress. Our results demonstrate HuR is a critical modulator for the regulation of stress-induced synaptic plasticity alterations and depression, providing a potential therapeutic target for the treatment of depressive disorders.