| Literature DB >> 35201886 |
Shi-Bin Li1,2, Valentina Martinez Damonte1,2, Chong Chen3,4, Gordon X Wang1, Justus M Kebschull5, Hiroshi Yamaguchi1,2, Wen-Jie Bian1,2, Carolin Purmann1,6, Reenal Pattni1,6, Alexander Eckehart Urban1,6, Philippe Mourrain1,7, Julie A Kauer1,2, Grégory Scherrer3,4, Luis de Lecea1,2.
Abstract
Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of Kcnq2/3 genes in Hcrt neurons of young mice destabilized sleep, mimicking aging-associated sleep fragmentation, whereas the KCNQ-selective activator flupirtine hyperpolarized Hcrt neurons and rejuvenated sleep architecture in aged mice. Our findings demonstrate a mechanism underlying sleep instability during aging and a strategy to improve sleep continuity.Entities:
Mesh：
Substances：
Year: 2022 PMID： 35201886 PMCID： PMC9107327 DOI： 10.1126/science.abh3021
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714