Work

A glial circadian gene expression atlas reveals cell-type and disease-specific reprogramming in response to amyloid pathology or aging

Year: 2025

Type: article

Abstract: While circadian rhythm disruption may promote neurodegenerative disease, how aging and neurodegenerative pathology impact circadian gene expression patterns in different brain cell types is unknown. Here, we used translating ribosome affinity purification methods to define the circadian translatomes of astrocytes, microglia, and bulk cerebral cortex, in healthy mouse brain and in the settings of amyloid-beta plaque pathology or aging. Our data reveal that glial circadian translatomes are highly cell type-specific and exhibit profound, context-dependent reprogramming of rhythmic transcripts in response to amyloid pathology or aging. Transcripts involved in glial activation, immunometabolism, and proteostasis, as well as nearly half of all Alzheimer Disease (AD)-associated risk genes, displayed circadian oscillations, many of which were altered by pathology. Amyloid-related differential gene expression was also dependent on time of day. Thus, circadian rhythms in gene expression are cell- and context dependent and provide important insights into glial gene regulation in health, AD, and aging.

Source: Nature Neuroscience

DOI: 10.1038/s41593-025-02067-1

Authors: Patrick W. Sheehan, Stuart B. Fass, Darshan Sapkota, Sylvia Kang, Henry C. Hollis, Jennifer H. Lawrence, Sohui Park, Ashish Sharma, Dorothy P. Schafer, Ron C. Anafi, Joseph D. Dougherty, John D. Fryer, Erik S. Musiek

Institutions: Washington University in St. Louis, The University of Texas at Dallas, Mayo Clinic in Florida, Drexel University, University of Massachusetts Chan Medical School, University of Pennsylvania, Translational Genomics Research Institute

Language: English

Topic: Circadian rhythm and melatonin

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $12,690

Funders: U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Cancer Institute, National Institute of Neurological Disorders and Stroke

Awards: G1380757792, Circadian Organization and Disorder in Alzheimer's Disease, Dissecting the impact of senescence on microglia function and neurodegeneration, ROLE OF GLIAL CIRCADIAN CLOCK DYSFUNCTION IN THE PATHOGENESIS OF ALZHEIMER'S DISEASE, G2794228280, G3439387492, G3733095065, G4238952269, G6147342941, G635252029, G7909356214, Neurobiological significance of Aqp4 stop codon readthrough, G9000033119, G9000259569, Multidisciplinary Training in Alzheimer and Related Dementias, Regulation of local translation in glia, Cancer Center Support Grant, Microglia-Astrocyte Crosstalk Regulating SynapseRemodeling

OpenAlex ID: W4415464656

FWCI: 8.867

Cites: 64

Cited by: 25

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