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REV-ERBalpha mediates complement expression and circadian regulation of microglial synaptic phagocytosis

Citation

Musiek, Erik (2020), REV-ERBalpha mediates complement expression and circadian regulation of microglial synaptic phagocytosis, Dryad, Dataset, https://doi.org/10.5061/dryad.nzs7h44p1

Abstract

The circadian clock has been shown to regulate various aspects of brain health including microglial and astrocyte activation. Here we report that deletion of the master clock protein BMAL1 induces robust increases in the expression of complement genes such as C3, C4b and C1q in the hippocampus. Loss of downstream REV-ERBa-mediated transcriptional repression led to increases in C4b in neurons and astrocytes as well as C3 protein in microglia and astrocytes. REV-ERBa deletion induced complement C3/C4b gene expression and increased microglial phagocytosis of synapses in the CA3 region of the hippocampus. Finally, we observed diurnal variation in the degree of microglial synaptic phagocytosis in wild type mice which was abrogated by REV-ERBα deletion. This work uncovers the BMAL1-REV-ERBa axis as a regulator of complement expression and synaptic phagocytosis in the brain, thereby illuminating a novel mechanism of synaptic regulation by the circadian clock.

Methods

The dataset is a GraphPad Prizm files with the raw data which constitutes each figure in the paper. The actual graphs are included in the file, along with the underlying data.  The data includes gene expression data (qPCR) from brain samples, as well as image quantification data. Raw images were confocal stacks (not included) which were analyzed with Imaris software, with the resulting data being put into the GraphPad file.

Funding

National Institute on Aging, Award: R01AG054517

Cure Alzheimer's Fund, Award: Investigator award

Coins for Alzheimer's Research Trust, Award: Investigator award

National Science Foundation, Award: DGE- 1745038