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.
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 version of the paper has not been formally peer reviewed.