Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain
| Autor: | Julia Tevini, Heimo Wolinski, Michael C. Bassik, Benoit Lehallier, Carolyn R. Bertozzi, Song E. Lee, Macy E. Zardeneta, John V. Pluvinage, Vidhu Mathur, Tony Wyss-Coray, David W. Morgens, Oliver Hahn, Thomas K. Felder, Ludwig Aigner, Julia Marschallinger, Michael S. Haney, Tal Iram, Justin Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Aging Phagocytosis Inflammation Biology Article Proinflammatory cytokine Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Lipid droplet medicine Aging brain Animals Humans 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Microglia General Neuroscience Neurodegeneration Brain medicine.disease Lipids Cell biology 030104 developmental biology medicine.anatomical_structure chemistry lipids (amino acids peptides and proteins) medicine.symptom Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience |
| DOI: | 10.1101/722827 |
| Popis: | Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call lipid droplet-accumulating microglia (LAM), are defective in phagocytosis, produce high levels of reactive oxygen species, and secrete pro-inflammatory cytokines. RNA sequencing analysis of LAM revealed a transcriptional profile driven by innate inflammation distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin, are causes of autosomal dominant forms of human neurodegenerative diseases. We thus propose that LAM contribute to age-related and genetic forms of neurodegeneration. |
| Databáze: | OpenAIRE |
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