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

23 Pages Posted: 13 Jul 2018 Sneak Peek Status: Published

See all articles by Brian V. Lananna

Brian V. Lananna

Washington University in St. Louis - Department of Neurology

Collin J. Nadarajah

Washington University in St. Louis - Department of Neurology

Mariko Izumo

University of Texas at Dallas - Department of Neuroscience

Michelle R. Cedeño

Washington University in St. Louis - Department of Neurology

David D. Xiong

Washington University in St. Louis - Department of Neurology

Julie Dimitry

Washington University in St. Louis - Department of Neurology

Chak Foon Tso

Washington University in St. Louis - Department of Biology

Celia A. McKee

Washington University in St. Louis - Department of Neurology

Percy Griffin

Washington University in St. Louis - Department of Neurology

Patrick W. Sheehan

Washington University in St. Louis - Department of Neurology

Jeffery A. Haspel

Washington University in St. Louis - Department of Medicine

Ben A. Barres

Stanford University - Department of Neurobiology

Shane A. Liddelow

University of Melbourne - Department of Pharmacology and Therapeutics

Joseph S. Takahashi

University of Texas at Dallas - Department of Neuroscience

Ilia N. Karatsoreos

Washington State University - Department of Integrative Physiology and Neuroscience

Erik S. Musiek

Washington University in St. Louis - Department of Neurology

More...

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 clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation 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 novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.

Suggested Citation

Lananna, Brian V. and Nadarajah, Collin J. and Izumo, Mariko and Cedeño, Michelle R. and Xiong, David D. and Dimitry, Julie and Tso, Chak Foon and McKee, Celia A. and Griffin, Percy 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., Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1 (2018). Available at SSRN: https://ssrn.com/abstract=3212831 or http://dx.doi.org/10.2139/ssrn.3212831
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Brian V. Lananna

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Collin J. Nadarajah

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Mariko Izumo

University of Texas at Dallas - Department of Neuroscience

United States

Michelle R. Cedeño

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

David D. Xiong

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Julie Dimitry

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Chak Foon Tso

Washington University in St. Louis - Department of Biology

One Brookings Drive
Campus Box 1208
Saint Louis, MO 63130-4899
United States

Celia A. McKee

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Percy Griffin

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Patrick W. Sheehan

Washington University in St. Louis - Department of Neurology

St. Louis, MO
United States

Jeffery A. Haspel

Washington University in St. Louis - Department of Medicine

St. Louis, MO 63110
United States

Ben A. Barres

Stanford University - Department of Neurobiology

Stanford, CA 94305
United States

Shane A. Liddelow

University of Melbourne - Department of Pharmacology and Therapeutics

Australia

Joseph S. Takahashi

University of Texas at Dallas - Department of Neuroscience

United States

Ilia N. Karatsoreos

Washington State University - Department of Integrative Physiology and Neuroscience

United States

Erik S. Musiek (Contact Author)

Washington University in St. Louis - Department of Neurology ( email )

St. Louis, MO
United States

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