Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells

• 成果类型: Article
• 署名作者: Liu, Qiang; Luo, Xing; Liang, Ziqi; Qin, Dezhe; Xu, Mingyue; Wang, Min; Guo, Weixiang
• 署名单位: Chinese Academy of Sciences; Institute of Genetics & Developmental Biology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13074
• DOI: 10.1073/pnas.2318030121
• 发表日期: 2024-02-20
• 关键词: gene-expression; locus-coeruleus; hippocampal neurogenesis; sleep; norepinephrine; neurons; cycle; mice

摘要

The circadian clock throughout the day organizes the activity of neural stem cells (NSCs) in the dentate gyrus (DG) of adult hippocampus temporally. However, it is still unclear whether and how circadian signals from the niches contribute to daily rhythmic variation of NSC activation. Here, we show that norepinephrinergic (NEergic) projections from the locus coeruleus (LC), a brain arousal system, innervate into adult DG, where daily rhythmic release of norepinephrine (NE) from the LC NEergic neurons controlled circadian variation of NSC activation through (33- adrenoceptors. Disrupted circadian rhythmicity by acute sleep deprivation leads to transient NSC overactivation and NSC pool exhaustion over time, which is effectively ameliorated by the inhibition of the LC NEergic neuronal activity or (33- adrenoceptors- mediated signaling. Finally, we demonstrate that NE/(33- adrenoceptors- mediated signaling regulates NSC activation through molecular clock BMAL1. Therefore, our study unravels that adult NSCs precisely coordinate circadian neural circuit and intrinsic molecular circadian clock to adapt their cellular behavior across the day.