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

Brian V. Lananna, Collin J. Nadarajah, Mariko Izumo, Michelle R. Cedeño, 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

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-9.e5
JournalCell Reports
Volume25
Issue number1
DOIs
StatePublished - Oct 2 2018

Keywords

  • Bmal1
  • astrocyte
  • astrogliosis
  • circadian
  • glutathione
  • neuroinflammation
  • rhythm

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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