Department of Anesthesiology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Neurology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Neurotoxicology. 2022 May;90:216-227. doi: 10.1016/j.neuro.2022.04.005. Epub 2022 Apr 18.
Postoperative cognitive dysfunction (POCD) is a major postoperative complication. Triggering receptor expressed on myeloid cells 2 (TREM2) exerts a neuroprotective function against neuro-inflammatory responses. The present study investigated the role of TREM2 in anesthesia and surgery-induced cognitive impairment and the potential related mechanism. Our results revealed that TREM2 was downregulated, coupled with activation of the NLRP3 inflammasome and subsequent IL-1β expression on postoperative day 3. A corresponding decline in PSD-95 and BDNF was found at the same time point. The key regulator of mitophagy PINK1 and Parkin protein levels were significantly decreased following surgery and anesthesia. TREM2 overexpression partially reversed postoperative cognitive impairment and enhanced PSD-95 and BDNF expression. TREM2 overexpression also improved mitophagy function and inhibited activation of the NLRP3 inflammasome and associated production of IL-1β. Our findings demonstrate that TREM2 rescues anesthesia and surgery-induced spatial learning and memory impairment and neuro-inflammation in aged C57/BL6 mice, which may be at least partially mediated through the activation of mitophagy and subsequent inhibition of the NLRP3 inflammasome.
术后认知功能障碍（POCD）是一种主要的术后并发症。髓样细胞触发受体 2（TREM2）发挥神经保护作用，对抗神经炎症反应。本研究探讨了 TREM2 在麻醉和手术引起的认知障碍中的作用及其潜在的相关机制。我们的结果表明，TREM2 在术后第 3 天下调，同时 NOD、LRP 和 caspase-1 炎症小体激活，随后白细胞介素-1β表达增加。与此同时，PSD-95 和脑源性神经营养因子表达下降。手术和麻醉后，线粒体自噬的关键调节因子 PINK1 和 Parkin 蛋白水平显著下降。TREM2 的过表达部分逆转了术后认知障碍，并增强了 PSD-95 和脑源性神经营养因子的表达。TREM2 的过表达还改善了线粒体自噬功能，并抑制了 NOD、LRP 和 caspase-1 炎症小体的激活及其相关白细胞介素-1β的产生。我们的研究结果表明，TREM2 可挽救老年 C57/BL6 小鼠麻醉和手术引起的空间学习和记忆损伤以及神经炎症，这至少部分是通过激活线粒体自噬和随后抑制 NOD、LRP 和 caspase-1 炎症小体来实现的。
