Dysregulation of miR-142 results in anxiety-like behaviors following single prolonged stress
Dysregulation of miR-142 results in anxiety-like behaviors following single prolonged stress
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DOI：
10.1016/j.bbr.2019.03.018
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发表时间：
2019-06-03
影响因子：
2.7
通讯作者：
Tong, Lei
中科院分区：
文献类型：
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作者：
Ji, Li -Li;Ye, Yao;Tong, Lei
创伤后应激障碍（PTSD）是一种普遍存在的精神障碍，被归类为创伤和压力相关障碍。虽然许多表观遗传因素与PTSD的风险有关，但这种疾病的确切机制尚不清楚。然而，越来越多的证据表明，microrna的失调与压力相关的精神疾病有关，导致焦虑样行为、记忆相关缺陷和异常的神经元可塑性。在这里，暴露于单次长时间应激的大鼠显示杏仁核中microRNA-142-5p水平增加，同时其预测目标Npas4水平降低，Npas4是一种活性调节的转录因子，与应激相关的精神病理有关。此外，暴露于单一长时间应激后，对microRNA-142的抑制表现出焦虑样行为和记忆缺陷的减少，以及Npas4和BDNF的表达增加。此外，双荧光素酶报告基因实验表明Npas4是miR-142的直接下游靶点。综上所述，这些数据表明miR-142可能在应激相关精神疾病的发病机制中发挥关键作用。
Posttraumatic stress disorder (PTSD) is a prevalent mental disorder that is classified as a trauma- and stressorrelated disorder. While numerous epigenetic factors are related to the risk for PTSD, the precise mechanisms underlying this disorder remain unclear. However, accumulating evidence has demonstrated that dysregulation of microRNAs is involved in stress-related psychiatric disorders, resulting in anxiety-like behavior, memoryrelated deficits and aberrant neuronal plasticity. Here, rats exposed to single prolonged stress showed increased microRNA-142-5p levels in the amygdala and a concurrent reduction in the levels of its predicted target Npas4, an activity-regulated transcription factor, which was implicated in stress-related psychopathologies. In addition, the inhibition of microRNA-142 following exposure to single prolonged stress exhibited decreased anxiety-like behaviors and memory deficits, as well as increased expression of Npas4 and BDNF. Furthermore, a dual-luciferase reporter assay indicated that Npas4 was a direct downstream target of miR-142. Taken together, these data suggest that miR-142 may play a key role in the pathogenesis of stress-related psychiatric disorders.