Xie Juhua, Han Fang, Shi Yuxiu
Laboratory of Post-Traumatic Stress Disorder, Department of Histology and Embryology, Institute of Pathology and Pathophysiology, Basic Medical Sciences College, China Medical University, 92 North 2nd Road, Shenyang, 110001, Liaoning Province, People's Republic of China.
Neurochem Res. 2014 Apr;39(4):741-7. doi: 10.1007/s11064-014-1262-x. Epub 2014 Mar 2.
The dorsal raphe nucleus (DRN) has been suggested playing an important role in the pathophysiology of post-traumatic stress disorder (PTSD), however the underlying cellular mechanisms are not fully understood. The endoplasmic reticulum (ER) is a critical organelle for synthesis of membrane and secretory proteins, and perturbations in ER lead to the unfolded protein response (UPR). In the present experiment, we hypothesized UPR may be associated with the PTSD, and there is an induction of UPR in the DRN neurons of the PTSD-like rats. We first observed the morphological changes of ER in the DRN neurons of the rats exposed to single-prolonged stress (SPS), a model of PTSD, and then we also detected the expression of ER chaperones glucose regulated protein 78 (GRP78) and glucose regulated protein (GRP94) which are two key sensors and mediators of the UPR and are considered an ER stress-specific inducible proteins using methods of western blot and immunohistochemical analysis. Our results demonstrated there were abnormal expansion of ER and up-regulation expression of GRP78 and GRP94 after SPS, which indicated that the UPR was triggered in the DRN neurons of the PTSD-like rats. These results are consistent with our speculation that UPR may be associated with the PTSD, and suggest us the UPR may be a new critical cellular mechanisms of PTSD.
背侧缝核(DRN)被认为在创伤后应激障碍(PTSD)的病理生理学中起重要作用,然而其潜在的细胞机制尚未完全明确。内质网(ER)是合成膜蛋白和分泌蛋白的关键细胞器,内质网紊乱会导致未折叠蛋白反应(UPR)。在本实验中,我们假设UPR可能与PTSD有关,且在创伤后应激障碍样大鼠的DRN神经元中存在UPR的诱导。我们首先观察了暴露于单次延长应激(SPS,一种PTSD模型)的大鼠DRN神经元内质网的形态变化,然后还使用蛋白质印迹法和免疫组织化学分析方法检测了内质网伴侣蛋白葡萄糖调节蛋白78(GRP78)和葡萄糖调节蛋白(GRP94)的表达,这两种蛋白是UPR的两个关键传感器和介质,被认为是内质网应激特异性诱导蛋白。我们的结果表明,SPS后内质网出现异常扩张,GRP78和GRP94表达上调,这表明创伤后应激障碍样大鼠的DRN神经元中触发了UPR。这些结果与我们的推测一致,即UPR可能与PTSD有关,并提示我们UPR可能是PTSD一种新的关键细胞机制。