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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Cell Death / physiology
  • Circadian Clocks / genetics
  • Circadian Clocks / physiology*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Primary Cell Culture
  • Transfection

Substances

  • ARNTL Transcription Factors
  • Arntl protein, mouse