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 journalArticle

8 Citations (Scopus)

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

Fingerprint

ARNTL Transcription Factors
Circadian Clocks
Astrocytes
Clocks
Chemical activation
Brain
Glutathione Transferase
Health
Neurodegenerative diseases
Brain Diseases
Gene expression
Neurodegenerative Diseases
Modulators
Neurons
Aging of materials
Gene Expression

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lananna, B. V., Nadarajah, C. J., Izumo, M., Cedeño, M. R., Xiong, D. D., Dimitry, J., ... Musiek, E. S. (2018). Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1. Cell Reports, 25(1), 1-9.e5. https://doi.org/10.1016/j.celrep.2018.09.015

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1. / Lananna, Brian V.; Nadarajah, Collin J.; Izumo, Mariko; Cedeño, Michelle R.; Xiong, David D.; Dimitry, Julie; Tso, Chak Foon; McKee, Celia A.; Griffin, Percy; Sheehan, Patrick W.; Haspel, Jeffery A.; Barres, Ben A.; Liddelow, Shane A.; Takahashi, Joseph S.; Karatsoreos, Ilia N.; Musiek, Erik S.

In: Cell Reports, Vol. 25, No. 1, 02.10.2018, p. 1-9.e5.

Research output: Contribution to journalArticle

Lananna, BV, Nadarajah, CJ, Izumo, M, Cedeño, MR, Xiong, DD, Dimitry, J, Tso, CF, McKee, CA, Griffin, P, Sheehan, PW, Haspel, JA, Barres, BA, Liddelow, SA, Takahashi, JS, Karatsoreos, IN & Musiek, ES 2018, 'Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1', Cell Reports, vol. 25, no. 1, pp. 1-9.e5. https://doi.org/10.1016/j.celrep.2018.09.015
Lananna BV, Nadarajah CJ, Izumo M, Cedeño MR, Xiong DD, Dimitry J et al. Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1. Cell Reports. 2018 Oct 2;25(1):1-9.e5. https://doi.org/10.1016/j.celrep.2018.09.015
Lananna, Brian V. ; Nadarajah, Collin J. ; Izumo, Mariko ; Cedeño, Michelle R. ; Xiong, David D. ; Dimitry, Julie ; Tso, Chak Foon ; McKee, Celia A. ; Griffin, Percy ; Sheehan, Patrick W. ; Haspel, Jeffery A. ; Barres, Ben A. ; Liddelow, Shane A. ; Takahashi, Joseph S. ; Karatsoreos, Ilia N. ; Musiek, Erik S. / Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1. In: Cell Reports. 2018 ; Vol. 25, No. 1. pp. 1-9.e5.
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