Journal article

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

Brian Lananna, Collin J Nadarajah, Mariko Izumo, Michelle R Cedeno, David D Xiong, Julie Dimitry, Chak Foon Tso, Celia A McKee, Percy Griffin, Patrick W Sheehan, Jeffery A Haspel, Ben A Barres, Shane A Liddelow, Joseph S Takahashi, Ilia N Karatsoreos, Erik S Musiek

Cell Reports | CELL PRESS | Published : 2018

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 deat..

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Grants

Awarded by NINDS


Awarded by NIA


Awarded by NSF CAREER award


Awarded by Australian National Health and Medical Research Council


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

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.