Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice

Background: 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 regulat...

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Main Authors: Pei-Chang Liu, Wei Yao, Xing-Yu Chen, Wei-Kun Su, Ze-Hong Zheng, Xiong-Bin Yan, Ya-Ling Deng, Kai-Ge Shi, Xin Liu, Yu-Wei Gao, Tian-Tian Lin, Yun-Xi Zhu, Ying-Xuan Lin, Zhong-Hua Zhu, Ping Cai, Liang-Cheng Zhang, Li Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.991238/full
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author Pei-Chang Liu
Wei Yao
Xing-Yu Chen
Wei-Kun Su
Ze-Hong Zheng
Xiong-Bin Yan
Ya-Ling Deng
Kai-Ge Shi
Xin Liu
Yu-Wei Gao
Tian-Tian Lin
Yun-Xi Zhu
Ying-Xuan Lin
Zhong-Hua Zhu
Ping Cai
Liang-Cheng Zhang
Li Chen
author_facet Pei-Chang Liu
Wei Yao
Xing-Yu Chen
Wei-Kun Su
Ze-Hong Zheng
Xiong-Bin Yan
Ya-Ling Deng
Kai-Ge Shi
Xin Liu
Yu-Wei Gao
Tian-Tian Lin
Yun-Xi Zhu
Ying-Xuan Lin
Zhong-Hua Zhu
Ping Cai
Liang-Cheng Zhang
Li Chen
author_sort Pei-Chang Liu
collection DOAJ
description Background: 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.Methods: 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.Results: 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.Conclusion: PBN astrocytes are a key neural substrate regulating wakefulness and emergence from isoflurane anesthesia.
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spelling doaj.art-f1592fa369b54cdda149eca7c6616fa02023-01-13T05:58:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-01-011310.3389/fphar.2022.991238991238Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in micePei-Chang Liu0Wei Yao1Xing-Yu Chen2Wei-Kun Su3Ze-Hong Zheng4Xiong-Bin Yan5Ya-Ling Deng6Kai-Ge Shi7Xin Liu8Yu-Wei Gao9Tian-Tian Lin10Yun-Xi Zhu11Ying-Xuan Lin12Zhong-Hua Zhu13Ping Cai14Liang-Cheng Zhang15Li Chen16Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, ChinaFujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, ChinaFujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaSchool of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, ChinaFujian Province Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou, Fujian, ChinaDepartment of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, ChinaBackground: 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.Methods: 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.Results: 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.Conclusion: PBN astrocytes are a key neural substrate regulating wakefulness and emergence from isoflurane anesthesia.https://www.frontiersin.org/articles/10.3389/fphar.2022.991238/fullparabrachial nucleiastrocytessleep-wakegeneral anesthesiaisoflurane
spellingShingle Pei-Chang Liu
Wei Yao
Xing-Yu Chen
Wei-Kun Su
Ze-Hong Zheng
Xiong-Bin Yan
Ya-Ling Deng
Kai-Ge Shi
Xin Liu
Yu-Wei Gao
Tian-Tian Lin
Yun-Xi Zhu
Ying-Xuan Lin
Zhong-Hua Zhu
Ping Cai
Liang-Cheng Zhang
Li Chen
Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
Frontiers in Pharmacology
parabrachial nuclei
astrocytes
sleep-wake
general anesthesia
isoflurane
title Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
title_full Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
title_fullStr Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
title_full_unstemmed Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
title_short Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
title_sort parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice
topic parabrachial nuclei
astrocytes
sleep-wake
general anesthesia
isoflurane
url https://www.frontiersin.org/articles/10.3389/fphar.2022.991238/full
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