Tan Xiaoxiang, Wang Jiajia, Yao Juan, Yuan Jing, Dai Yuchen, Sun Menghan, Zhang Tianhao, Yang Jiaojiao, Cai Wenlan, Qiu Lili, Sun Jie
Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, the School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, the School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
Neurosci Lett. 2023 Feb 6;796:137049. doi: 10.1016/j.neulet.2023.137049. Epub 2023 Jan 3.
Elderly patients after surgery are prone to cognitive decline known as postoperative cognitive dysfunction (POCD). Several studies have shown that the microglial activation and the increase of complement protein expression in hippocampus induced by surgery may be related to the pathogenesis of POCD. The purpose of this study was to determine whether microglia and complement system were involved in cognitive dysfunction in aged mice.
The POCD model was established by exploratory laparotomy in 15-month-old male C57BL/6J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Minocycline was used to suppress the activation of microglia, and complement 3 receptor inhibitor was used to suppress the association between microglia and complement 3. Western blot and immunofluorescence were used to detect the microglial activation, complement protein, and synaptic protein expressions.
Operation induced hippocampal-dependent memory impairment (P < 0.01), which was accompanied by microglial activation (P < 0.01). There was also a significant reduction in inhibitory synaptic protein expression in the hippocampus of mice in the surgery group (P < 0.01). However, minocycline, a microglia inhibitor, rescued all the above changes. In addition, C3RI intervention inhibited the phagocytosis of inhibitory synapses by microglia (P < 0.05) and improved the cognitive function of mice (P < 0.01).
Microglia participate in postoperative cognitive dysfunction by mediating inhibitory synaptic loss through the complement pathway.
术后老年患者容易出现认知功能下降，即术后认知功能障碍（POCD）。多项研究表明，手术诱导的海马体小胶质细胞激活和补体蛋白表达增加可能与POCD的发病机制有关。本研究的目的是确定小胶质细胞和补体系统是否参与老年小鼠的认知功能障碍。
通过对15月龄雄性C57BL/6J小鼠进行剖腹探查建立POCD模型，并进行动物行为测试以检测海马依赖性记忆能力。使用米诺环素抑制小胶质细胞的激活，并使用补体3受体抑制剂抑制小胶质细胞与补体3之间的关联。采用蛋白质免疫印迹法和免疫荧光法检测小胶质细胞激活、补体蛋白和突触蛋白的表达。
手术诱导了海马依赖性记忆障碍（P < 0.01），同时伴有小胶质细胞激活（P < 0.01）。手术组小鼠海马中抑制性突触蛋白表达也显著降低（P < 0.01）。然而，小胶质细胞抑制剂米诺环素挽救了上述所有变化。此外，C3RI干预抑制了小胶质细胞对抑制性突触的吞噬作用（P < 0.05），并改善了小鼠的认知功能（P < 0.01）。
小胶质细胞通过补体途径介导抑制性突触丢失参与术后认知功能障碍。
