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Cell Rep. 2018 Oct 2;25(1):1-9.e5. doi: 10.1016/j.celrep.2018.09.015.

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1.

Author information

1
Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA.
2
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3
Department of Biology, Washington University, St. Louis, MO, USA.
4
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
5
Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USA.
6
Neuroscience Institute, Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY, USA; Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, VIC, Australia.
7
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
8
Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
9
Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: musieke@wustl.edu.

Abstract

Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults and plays a critical role in brain health and disease. We report that the core circadian clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism and a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation and inflammatory gene expression in vitro and in vivo, mediated in part by suppression of glutathione-S-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a mechanism by which the circadian clock could influence many aspects of brain function and neurological disease.

KEYWORDS:

Bmal1; astrocyte; astrogliosis; circadian; glutathione; neuroinflammation; rhythm

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