Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Exp Neurol. 2022 Oct;356:114154. doi: 10.1016/j.expneurol.2022.114154. Epub 2022 Jun 24.
MicroRNA-124-3p (miR-124) plays an important role in neuroprotective functions in various neurological disorders, but whether miR-124 participates in the pathological progression of posttraumatic stress disorder (PTSD) remains poorly understood.
In the present study, we assessed the level of neuroinflammation in the hippocampus of rats exposed to single-prolonged stress (SPS) by Western blot and immunofluorescence staining, while the effect of miR-124 on PTSD-like behaviors was evaluated by behavioral test.
Our results showed that the level of miR-124 in the hippocampus of rats exposed to SPS was downregulated and that the upregulation of miR-124 could alleviate the PTSD-like behaviors of SPS rats. This effect of miR-124 might be achieved through TNF receptor-associated Factor 6 (TRAF6), which is a target gene of miR-124 and plays an important role in the immune and inflammatory reaction by regulating nuclear factor kappa-B (NF-κB). Furthermore, we found that miR-124 not only decreased the level of proinflammatory cytokines but also increased the expression levels of synaptic proteins (PSD95 and synapsin I) and regulated the morphology of neurons.
These results suggested that miR-124 might attenuate PTSD-like behaviors and decrease the level of proinflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats exposed to SPS.
MicroRNA-124-3p(miR-124)在各种神经紊乱的神经保护功能中发挥着重要作用,但 miR-124 是否参与创伤后应激障碍(PTSD)的病理进展尚不清楚。
在本研究中,我们通过 Western blot 和免疫荧光染色评估了单延长应激(SPS)暴露的大鼠海马中的神经炎症水平,同时通过行为测试评估了 miR-124 对 PTSD 样行为的影响。
我们的结果表明,SPS 暴露大鼠海马中的 miR-124 水平下调,而 miR-124 的上调可以减轻 SPS 大鼠的 PTSD 样行为。miR-124 的这种作用可能是通过 TNF 受体相关因子 6(TRAF6)实现的,TRAF6 是 miR-124 的靶基因,通过调节核因子 kappa-B(NF-κB)在免疫和炎症反应中发挥重要作用。此外,我们发现 miR-124 不仅降低了促炎细胞因子的水平,还增加了突触蛋白(PSD95 和 synapsin I)的表达水平,并调节了神经元的形态。
这些结果表明,miR-124 可能通过下调 SPS 暴露大鼠海马中 TRAF6 的表达来减轻 PTSD 样行为并降低促炎细胞因子的水平。