Jiwaji Zoeb, Márkus Nóra M, McQueen Jamie, Emelianova Katie, He Xin, Dando Owen, Chandran Siddharthan, Hardingham Giles E
UK Dementia Research Institute, Edinburgh Medical School, The University of Edinburgh, Edinburgh, United Kingdom.
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Front Netw Physiol. 2023 Aug 21;3:1216366. doi: 10.3389/fnetp.2023.1216366. eCollection 2023.
General anesthesia represents a common clinical intervention and yet can result in long-term adverse CNS effects particularly in the elderly or dementia patients. Suppression of cortical activity is a key feature of the anesthetic-induced unconscious state, with activity being a well-described regulator of pathways important for brain health. However, the extent to which the effects of anesthesia go beyond simple suppression of neuronal activity is incompletely understood. We found that general anesthesia lowered cortical expression of genes induced by physiological activity , and recapitulated additional patterns of gene regulation induced by total blockade of firing activity , including repression of neuroprotective genes and induction of pro-apoptotic genes. However, the influence of anesthesia extended beyond that which could be accounted for by activity modulation, including the induction of non activity-regulated genes associated with inflammation and cell death. We next focused on astrocytes, important integrators of both neuronal activity and inflammatory signaling. General anesthesia triggered gene expression changes consistent with astrocytes being in a low-activity environment, but additionally caused induction of a reactive profile, with transcriptional changes enriched in those triggered by stroke, neuroinflammation, and Aß/tau pathology. Thus, while the effects of general anesthesia on cortical gene expression are consistent with the strong repression of brain activity, further deleterious effects are apparent including a reactive astrocyte profile.
全身麻醉是一种常见的临床干预措施，但可能会导致长期的中枢神经系统不良影响，尤其是在老年人或痴呆患者中。抑制皮层活动是麻醉诱导的无意识状态的一个关键特征，而活动是对大脑健康重要的通路的一个众所周知的调节因子。然而，麻醉的影响超出简单的神经元活动抑制的程度尚未完全了解。我们发现全身麻醉降低了由生理活动诱导的基因的皮层表达，并重现了由放电活动完全阻断诱导的其他基因调控模式，包括神经保护基因的抑制和促凋亡基因的诱导。然而，麻醉的影响超出了可以由活动调节解释的范围，包括诱导与炎症和细胞死亡相关的非活动调节基因。接下来，我们关注星形胶质细胞，它是神经元活动和炎症信号的重要整合者。全身麻醉引发的基因表达变化与星形胶质细胞处于低活动环境一致，但此外还导致了一种反应性特征的诱导，转录变化在由中风、神经炎症和Aβ/ tau病理引发的变化中富集。因此，虽然全身麻醉对皮层基因表达的影响与大脑活动的强烈抑制一致，但进一步的有害影响也很明显，包括反应性星形胶质细胞特征。
