Department of Physiology and Neurobiology, University of Connecticut, Storrs CT, USA.
School of Neuroscience, Virginia Polytechnic and State University, Blacksburg, VA, USA.
Curr Neuropharmacol. 2022;20(1):5-15. doi: 10.2174/1570159X19666210215120755.
General anesthetics are a mainstay of modern medicine, and although much progress has been made towards identifying molecular targets of anesthetics and neural networks contributing to endpoints of general anesthesia, our understanding of how anesthetics work remains unclear. Reducing this knowledge gap is of fundamental importance to prevent unwanted and life-threatening side-effects associated with general anesthesia. General anesthetics are chemically diverse, yet they all have similar behavioral endpoints, and so for decades, research has sought to identify a single underlying mechanism to explain how anesthetics work. However, this effort has given way to the 'multiple target hypothesis' as it has become clear that anesthetics target many cellular proteins, including GABAA receptors, glutamate receptors, voltage-independent K+ channels, and voltagedependent K+, Ca2+ and Na+ channels, to name a few. Yet, despite evidence that astrocytes are capable of modulating multiple aspects of neural function and express many anesthetic target proteins, they have been largely ignored as potential targets of anesthesia. The purpose of this brief review is to highlight the effects of anesthetic on astrocyte processes and identify potential roles of astrocytes in behavioral endpoints of anesthesia (hypnosis, amnesia, analgesia, and immobilization).
全身麻醉是现代医学的主要支柱,尽管在确定麻醉剂的分子靶点和参与全身麻醉终点的神经网络方面已经取得了很大进展,但我们对麻醉剂如何发挥作用的理解仍不清楚。缩小这一知识差距对于防止与全身麻醉相关的不必要和危及生命的副作用至关重要。全身麻醉剂种类繁多,但它们都有相似的行为终点,因此几十年来,研究一直致力于寻找一种单一的潜在机制来解释麻醉剂的作用方式。然而,随着人们越来越清楚地认识到麻醉剂靶向许多细胞蛋白,包括 GABA A 受体、谷氨酸受体、电压门控 K+通道和电压门控 K+、Ca2+和 Na+通道等,这种努力已经让位于“多靶点假说”。然而,尽管有证据表明星形胶质细胞能够调节神经功能的多个方面,并表达许多麻醉剂靶点蛋白,但它们作为麻醉潜在靶点在很大程度上被忽视了。本综述的目的是强调麻醉剂对星形胶质细胞过程的影响,并确定星形胶质细胞在麻醉行为终点(催眠、遗忘、镇痛和固定)中的潜在作用。