1. Academic Validation
  2. P2X7 Receptor in microglia contributes to propofol-induced unconsciousness by regulating synaptic plasticity in mice

P2X7 Receptor in microglia contributes to propofol-induced unconsciousness by regulating synaptic plasticity in mice

  • Neuroscience. 2023 May 19;S0306-4522(23)00223-3. doi: 10.1016/j.neuroscience.2023.05.012.
Bo Zhang 1 Panpan Zhang 2 Tingting L 3 Yue Cao 3 Ting Chen 3 Chang Chen 3 Zongze Zhang 4 Qi Zhong 5
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430022.
  • 2 Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei, China, 430071; Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, 430022.
  • 3 Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei, China, 430071.
  • 4 Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei, China, 430071. Electronic address: zhangzz@whu.edu.cn.
  • 5 Department of Anesthesiology, Zhongnan Hospital, Wuhan University, East Lake Road, Wuhan, Hubei, China, 430071. Electronic address: 200732180224@whu.edu.cn.
Abstract

Propofol infusion is processed through the wake-sleep cycle in neural connections, and the ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and synaptic plasticity through its regulation of electric activity in the brain. Here, we explored the potential roles of P2X7R of microglia in propofol-induced unconsciousness. Propofol induced loss of the righting reflex in male C57BL/6 wild-type mice and increased spectral power of the slow wave and delta wave of the medial prefrontal cortex (mPFC), all of which were reversed with P2X7R antagonist A-740003 and strengthened with P2X7R agonist Bz-ATP. Propofol increased the P2X7R expression level and P2X7R immunoreactivity with microglia in the mPFC, induced mild synaptic injury and increased GABA release in the mPFC, and these changes were less severe when treated with A-740003 and were more obvious when treated with Bz-ATP. Electrophysiological approaches showed that propofol induced a decreased frequency of sEPSCs and an increased frequency of sIPSCs, A-740003 decrease frequency of sEPSCs and sIPSCs and Bz-ATP increase frequency of sEPSCs and sIPSCs under propofol anesthesia. These findings indicated that P2X7R in microglia regulates synaptic plasticity and may contribute to propofol-mediated unconsciousness.

Keywords

P2X7 receptor; microglia; propofol; synaptic plasticity; unconsciousness.

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