2. Academic Validation
  3. Microglia participate in postoperative cognitive dysfunction by mediating the loss of inhibitory synapse through the complement pathway

Microglia participate in postoperative cognitive dysfunction by mediating the loss of inhibitory synapse through the complement pathway

  • Neurosci Lett. 2023 Feb 6;796:137049. doi: 10.1016/j.neulet.2023.137049.
Xiaoxiang Tan 1,  Jiajia Wang 1,  Juan Yao 1,  Jing Yuan 1,  Yuchen Dai 1,  Menghan Sun 1,  Tianhao Zhang 1,  Jiaojiao Yang 1,  Wenlan Cai 1,  Lili Qiu 2,  Jie Sun 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, the School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
  • 2 Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, the School of Medicine, Southeast University, Nanjing, Jiangsu Province, China. Electronic address: [email protected].
  • 3 Department of Anesthesiology, Surgery and Pain Management, Zhongda Hospital, the School of Medicine, Southeast University, Nanjing, Jiangsu Province, China. Electronic address: [email protected].
PMID: 36608926 DOI: 10.1016/j.neulet.2023.137049
Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: Microglia participate in postoperative cognitive dysfunction by mediating inhibitory synaptic loss through the complement pathway.

Keywords

Complement; Inhibitory synapse; Microglia; Postoperative cognitive dysfunction.

Figures
Products