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

First Author  Liu Q Year  2024
Journal  Proc Natl Acad Sci U S A Volume  121
Issue  8 Pages  e2318030121
PubMed ID  38346182 Mgi Jnum  J:353296
Mgi Id  MGI:7710854 Doi  10.1073/pnas.2318030121
Citation  Liu Q, et al. (2024) Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells. Proc Natl Acad Sci U S A 121(8):e2318030121
abstractText  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 beta3-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 beta3-adrenoceptors-mediated signaling. Finally, we demonstrate that NE/beta3-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.
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