Journal article
Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1
Cell reports (Cambridge), Vol.25(1), pp.1-9.e5
10/02/2018
Handle:
https://hdl.handle.net/2376/101598
PMCID: PMC6221830
PMID: 30282019
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.
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•Circadian disruption promotes astrocyte activation•Astrocyte-specific deletion of the circadian clock gene BMAL1 induces activation•BMAL1 regulates astrocyte activation by altering glutathione-S-transferase signaling•Loss of astrocyte BMAL1 enhances neuronal cell death in a co-culture system
Lananna et al. show that the circadian clock protein BMAL1 regulates astrocyte activation via a cell-autonomous mechanism involving diminished glutathione-S-transferase signaling. This finding elucidates a function of the core circadian clock in astrocytes and reveals BMAL1 as a modulator of astrogliosis.
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Details
- Title
- Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1
- Creators
- Brian V Lananna - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USACollin J Nadarajah - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USAMariko Izumo - Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USAMichelle R Cedeño - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USADavid D Xiong - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USAJulie Dimitry - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USAChak Foon Tso - Department of Biology, Washington University, St. Louis, MO, USACelia A McKee - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USAPercy Griffin - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USAPatrick W Sheehan - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USAJeffery A Haspel - Department of Medicine, Washington University School of Medicine, St. Louis, MO, USABen A Barres - Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USAShane A Liddelow - Neuroscience Institute, Department of Neuroscience and Physiology, NYU Langone Medical Center, New York, NY, USAJoseph S Takahashi - Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USAIlia N Karatsoreos - Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, Pullman, WA, USAErik S Musiek - Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
- Publication Details
- Cell reports (Cambridge), Vol.25(1), pp.1-9.e5
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier Inc
- Identifiers
- 99900546700101842
- Language
- English
- Resource Type
- Journal article