Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China.
School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, China.
Elife. 2023 Dec 22;12:RP92252. doi: 10.7554/eLife.92252.
General anesthesia leads to a loss of consciousness and an unrousable state in patients. Although general anesthetics are widely used in clinical practice, their underlying mechanisms remain elusive. The potential involvement of nonneuronal cells is unknown. Microglia are important immune cells in the central nervous system (CNS) that play critical roles in CNS function and dysfunction. We unintentionally observed delayed anesthesia induction and early anesthesia emergence in microglia-depleted mice. We found that microglial depletion differentially regulates neuronal activities by suppressing the neuronal network of anesthesia-activated brain regions and activating emergence-activated brain regions. Thus, microglia facilitate and stabilize the anesthesia status. This influence is not mediated by dendritic spine plasticity. Instead, it relies on the activation of microglial P2Y12 and subsequent calcium influx, which facilitates the general anesthesia response. Together, we elucidate the regulatory role of microglia in general anesthesia, extending our knowledge of how nonneuronal cells modulate neuronal activities.
全身麻醉会导致患者失去意识和无法唤醒的状态。尽管全身麻醉在临床实践中被广泛应用，但它们的潜在机制仍难以捉摸。非神经元细胞的潜在参与尚不清楚。小胶质细胞是中枢神经系统（CNS）中的重要免疫细胞，在 CNS 功能和功能障碍中发挥关键作用。我们意外地观察到小胶质细胞耗竭小鼠的麻醉诱导延迟和早期麻醉苏醒。我们发现，小胶质细胞耗竭通过抑制麻醉激活脑区的神经元网络和激活苏醒激活脑区来差异调节神经元活动。因此，小胶质细胞促进并稳定麻醉状态。这种影响不是通过树突棘可塑性介导的。相反，它依赖于小胶质细胞 P2Y12 的激活和随后的钙内流，这有助于全身麻醉反应。总的来说，我们阐明了小胶质细胞在全身麻醉中的调节作用，扩展了我们对非神经元细胞如何调节神经元活动的认识。
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