Adenosine-Dependent Arousal Induced by Astrocytes in a Brainstem Circuit.

Autor: Zhu Y; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China., Ma J; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China., Li Y; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China., Gu M; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China., Feng X; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China., Shao Y; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China., Tan L; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China., Lou HF; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China., Sun L; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China., Liu Y; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China., Zeng LH; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China., Qiu Z; Department of Neurology, Songjiang Hospital, Songjiang Research Institute, MOE-Shanghai Key Laboratory for Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China., Li XM; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China.; Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China., Duan S; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China.; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China.; Department of Neurology, Songjiang Hospital, Songjiang Research Institute, MOE-Shanghai Key Laboratory for Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China., Yu YQ; Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, 311121, China.; Nanhu Brain-computer Interface Institute, Hangzhou, 311100, China.; Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Nov 04, pp. e2407706. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1002/advs.202407706
Abstrakt: Astrocytes play a crucial role in regulating sleep-wake behavior. However, how astrocytes govern a specific sleep-arousal circuit remains unknown. Here, the authors show that parafacial zone (PZ) astrocytes responded to sleep-wake cycles with state-differential Ca 2+ activity, peaking during transitions from sleep to wakefulness. Using chemogenetic and optogenetic approaches, they find that activating PZ astrocytes elicited and sustained wakefulness by prolonging arousal episodes while impeding transitions from wakefulness to non-rapid eye movement (NREM) sleep. Activation of PZ astrocytes specially induced the elevation of extracellular adenosine through the ATP hydrolysis pathway but not equilibrative nucleoside transporter (ENT) mediated transportation. Strikingly, the rise in adenosine levels induced arousal by activating A 1 receptors, suggesting a distinct role for adenosine in the PZ beyond its conventional sleep homeostasis modulation observed in the basal forebrain (BF) and cortex. Moreover, at the circuit level, PZ astrocyte activation induced arousal by suppressing the GABA release from the PZ GABA neurons, which promote NREM sleep and project to the parabrachial nucleus (PB). Thus, their study unveils a distinctive arousal-promoting effect of astrocytes within the PZ through extracellular adenosine and elucidates the underlying mechanism at the neural circuit level.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: