Yang Luodong, Xing Wenlong, Shi Yan, Hu Min, Li Bin, Hu Yuanyuan, Zhang Guiqing
First Affiliated Hospital of Shihezi University, Shihezi, China.
Shihezi University, Shihezi, China.
Neuroscience. 2024 Sep 13;555:156-166. doi: 10.1016/j.neuroscience.2024.07.028. Epub 2024 Jul 21.
Inflammatory and myelin changes may contribute to the pathophysiology of post-traumatic stress disorder (PTSD). The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3), a brain inflammasome, is activated in the hippocampus of mice with PTSD. In other psychiatric disorders, NLRP3 expression has been associated with axonal myelination and demyelination. However, the association between NLRP3 and myelin in rats with PTSD remains unclear. Therefore, this study aims to investigate the relationship between the NLRP3 inflammasome and myelin in the hippocampus of rats with PTSD. A rat model of post-traumatic stress disorder was established using the single-prolonged stress (SPS) approach. Hippocampal tissues were collected for the detection of NLRP3 inflammasome-associated proteins and myelin basic protein at 3, 7, and 14 days after SPS. To further explore the relationship between NLRP3 and myelin, the NLRP3-specific inhibitor MCC950 was administered intraperitoneally to rats starting 72 h before SPS, and then alterations in NLRP3 inflammasome-associated proteins and myelin were observed in the PTSD and control groups. We found that NLRP3 and downstream related proteins were activated in the hippocampus of rats 3 days after SPS, and the myelin content in the hippocampus increased after SPS stress. MCC950 reduced the expression of NLRP3-related pathway proteins, improved anxiety behaviour and spatial learning memory impairment, and inhibited the increase in myelin content in the hippocampal region of rats after SPS. In conclusion the study indicates that NLRP3 has a significant role in the hippocampal region of rats with PTSD. Inhibition of the NLRP3 inflammasome could be a potential target for treating PTSD.
炎症和髓鞘变化可能促成创伤后应激障碍（PTSD）的病理生理学过程。含吡喃结构域的NOD样受体家族蛋白3（NLRP3）作为一种脑内炎性小体，在患创伤后应激障碍的小鼠海马体中被激活。在其他精神疾病中，NLRP3的表达与轴突髓鞘形成和脱髓鞘有关。然而，创伤后应激障碍大鼠中NLRP3与髓鞘之间的关联仍不清楚。因此，本研究旨在探讨创伤后应激障碍大鼠海马体中NLRP3炎性小体与髓鞘之间的关系。采用单次延长应激（SPS）方法建立创伤后应激障碍大鼠模型。在SPS后3天、7天和14天收集海马组织，检测NLRP3炎性小体相关蛋白和髓鞘碱性蛋白。为进一步探究NLRP3与髓鞘之间的关系，在SPS前72小时开始对大鼠腹腔注射NLRP3特异性抑制剂MCC950，然后观察创伤后应激障碍组和对照组中NLRP3炎性小体相关蛋白和髓鞘的变化。我们发现，SPS后3天大鼠海马体中的NLRP3及其下游相关蛋白被激活，SPS应激后海马体中的髓鞘含量增加。MCC950降低了NLRP3相关信号通路蛋白的表达，改善了焦虑行为和空间学习记忆障碍，并抑制了SPS后大鼠海马区髓鞘含量的增加。总之，该研究表明NLRP3在创伤后应激障碍大鼠的海马区中起重要作用。抑制NLRP3炎性小体可能是治疗创伤后应激障碍的一个潜在靶点。
