Liu Pei-Chang, Yao Wei, Chen Xing-Yu, Su Wei-Kun, Zheng Ze-Hong, Yan Xiong-Bin, Deng Ya-Ling, Shi Kai-Ge, Liu Xin, Gao Yu-Wei, Lin Tian-Tian, Zhu Yun-Xi, Lin Ying-Xuan, Zhu Zhong-Hua, Cai Ping, Zhang Liang-Cheng, Chen Li
Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Fujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.
Front Pharmacol. 2023 Jan 13;13:991238. doi: 10.3389/fphar.2022.991238. eCollection 2022.
The parabrachial nucleus (PBN) is an important structure regulating the sleep-wake behavior and general anesthesia. Astrocytes in the central nervous system modulate neuronal activity and consequential behavior. However, the specific role of the parabrachial nucleus astrocytes in regulating the sleep-wake behavior and general anesthesia remains unclear. We used chemogenetic approach to activate or inhibit the activity of PBN astrocytes by injecting AAV-GFAabc1d-hM3Dq-eGFP or AAV-GFAabc1d-hM4Di-eGFP into the PBN. We investigated the effects of intraperitoneal injection of CNO or vehicle on the amount of wakefulness, NREM sleep and REM sleep in sleep-wake behavior, and on the time of loss of righting reflex, time of recovery of righting reflex, sensitivity to isoflurane, electroencephalogram (EEG) power spectrum and burst suppression ratio (BSR) in isoflurane anesthesia. The activation of PBN astrocytes increased wakefulness amount for 4 h, while the inhibition of PBN astrocytes decreased total amount of wakefulness during the 3-hour post-injection period. Chemogenetic activation of PBN astrocytes decreased isoflurane sensitivity and shortened the emergence time from isoflurane-induced general anesthesia. Cortical EEG recordings revealed that PBN astrocyte activation decreased the EEG delta power and BSR during isoflurane anesthesia. Chemogenetic Inhibition of PBN astrocytes increased the EEG delta power and BSR during isoflurane anesthesia. PBN astrocytes are a key neural substrate regulating wakefulness and emergence from isoflurane anesthesia.
臂旁核（PBN）是调节睡眠-觉醒行为和全身麻醉的重要结构。中枢神经系统中的星形胶质细胞调节神经元活动及相应行为。然而，臂旁核星形胶质细胞在调节睡眠-觉醒行为和全身麻醉中的具体作用仍不清楚。我们采用化学遗传学方法，通过向臂旁核注射AAV-GFAabc1d-hM3Dq-eGFP或AAV-GFAabc1d-hM4Di-eGFP来激活或抑制臂旁核星形胶质细胞的活性。我们研究了腹腔注射氯氮平氮氧化物（CNO）或赋形剂对睡眠-觉醒行为中觉醒量、非快速眼动睡眠和快速眼动睡眠量的影响，以及对异氟烷麻醉中翻正反射消失时间、翻正反射恢复时间、对异氟烷的敏感性、脑电图（EEG）功率谱和爆发抑制率（BSR）的影响。激活臂旁核星形胶质细胞可使觉醒量增加4小时，而抑制臂旁核星形胶质细胞则会使注射后3小时内的总觉醒量减少。化学遗传学激活臂旁核星形胶质细胞可降低异氟烷敏感性，并缩短异氟烷诱导的全身麻醉后的苏醒时间。皮层脑电图记录显示，在异氟烷麻醉期间，臂旁核星形胶质细胞激活可降低脑电图δ波功率和爆发抑制率。化学遗传学抑制臂旁核星形胶质细胞可增加异氟烷麻醉期间的脑电图δ波功率和爆发抑制率。臂旁核星形胶质细胞是调节觉醒和异氟烷麻醉苏醒的关键神经基质。
