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Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
P2X7 Receptor in Microglia Contributes to Propofol-induced Unconsciousness by Regulating Synaptic Plasticity in Mice
Bo Zhang1, Panpan Zhang2, Tingting Li3
1Department of Anesthesiology, Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China.
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.
Insights
The purine type 2X7 receptor (P2X7R) in microglia plays a role in propofol-induced unconsciousness. Targeting P2X7R influences synaptic plasticity and brain activity during anesthesia.
Area of Science:
- Neuroscience
- Anesthesiology
- Cell Biology
Background:
- Propofol is a common anesthetic affecting the central nervous system.
- The P2X7 receptor (P2X7R) is involved in neural regulation and synaptic plasticity.
- Microglia, the brain's immune cells, express P2X7R and may influence anesthetic effects.
Purpose of the Study:
- To investigate the role of microglial P2X7R in propofol-induced unconsciousness.
- To determine how P2X7R activation or inhibition affects neural activity and synaptic function under propofol anesthesia.
Main Methods:
- Used male C57BL/6 wild-type mice undergoing propofol anesthesia.
- Administered P2X7R antagonist (A-740003) and agonist (Bz-ATP).
- Analyzed electroencephalogram (EEG) spectral power, P2X7R expression, synaptic markers, GABA release, and synaptic currents (sEPSCs, sIPSCs) in the medial prefrontal cortex (mPFC).
Main Results:
- Propofol induced loss of righting reflex, increased slow/delta wave activity, elevated P2X7R expression in microglia, mild synaptic injury, and increased GABA release in the mPFC.
- P2X7R antagonist reversed propofol's effects, while the agonist strengthened them.
- Propofol decreased sEPSCs and increased sIPSCs; A-740003 decreased both, while Bz-ATP increased both under propofol.
Conclusions:
- Microglial P2X7R is a key regulator of synaptic plasticity.
- P2X7R activity contributes to the mechanisms underlying propofol-mediated unconsciousness.
- Modulating P2X7R offers a potential target for managing anesthetic effects.
