@article{478dbb7e120c4734b474bd2f4c75203b,
title = "Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1",
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. 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.",
keywords = "Bmal1, astrocyte, astrogliosis, circadian, glutathione, neuroinflammation, rhythm",
author = "Lananna, {Brian V.} and Nadarajah, {Collin J.} and Mariko Izumo and Cede{\~n}o, {Michelle R.} and Xiong, {David D.} and Julie Dimitry and Tso, {Chak Foon} and McKee, {Celia A.} and Percy Griffin and Sheehan, {Patrick W.} and Haspel, {Jeffery A.} and Barres, {Ben A.} and Liddelow, {Shane A.} and Takahashi, {Joseph S.} and Karatsoreos, {Ilia N.} and Musiek, {Erik S.}",
note = "Funding Information: This study was funded by NINDS grant K08NS079405 (E.S.M.), NIA grants R01AG054517 (E.S.M.) and R21AG050054 (I.N.K.), NSF CAREER award 1553067 (I.N.K.), and an Alzheimer's Association New Investigator Award (E.S.M.). J.S.T. is an Investigator at the Howard Hughes Medical Institute. S.A.L. was supported by the Australian National Health and Medical Research Council (GNT1052961), the Glenn Foundation Glenn Award, an anonymous donation, and V. and S. Coates. Funding Information: This study was funded by NINDS grant K08NS079405 (E.S.M.), NIA grants R01AG054517 (E.S.M.) and R21AG050054 (I.N.K.), NSF CAREER award 1553067 (I.N.K.), and an Alzheimer's Association New Investigator Award (E.S.M.). J.S.T. is an Investigator at the Howard Hughes Medical Institute . S.A.L. was supported by the Australian National Health and Medical Research Council ( GNT1052961 ), the Glenn Foundation Glenn Award, an anonymous donation, and V. and S. Coates. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = oct,
day = "2",
doi = "10.1016/j.celrep.2018.09.015",
language = "English",
volume = "25",
pages = "1--9.e5",
journal = "Cell Reports",
issn = "2211-1247",
number = "1",
}