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Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain.
Marschallinger, Julia; Iram, Tal; Zardeneta, Macy; Lee, Song E; Lehallier, Benoit; Haney, Michael S; Pluvinage, John V; Mathur, Vidhu; Hahn, Oliver; Morgens, David W; Kim, Justin; Tevini, Julia; Felder, Thomas K; Wolinski, Heimo; Bertozzi, Carolyn R; Bassik, Michael C; Aigner, Ludwig; Wyss-Coray, Tony.
Affiliation
  • Marschallinger J; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Iram T; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
  • Zardeneta M; Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
  • Lee SE; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Lehallier B; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
  • Haney MS; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Pluvinage JV; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
  • Mathur V; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Hahn O; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
  • Morgens DW; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Kim J; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
  • Tevini J; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Felder TK; Department of Genetics, School of Medicine, and Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA.
  • Wolinski H; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Bertozzi CR; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
  • Bassik MC; Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Aigner L; Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
  • Wyss-Coray T; Paul F. Glenn Center for the Biology of Aging, Stanford University School of Medicine, Stanford, CA, USA.
Nat Neurosci ; 23(2): 194-208, 2020 02.
Article in En | MEDLINE | ID: mdl-31959936
ABSTRACT
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' (LDAM), are defective in phagocytosis, produce high levels of reactive oxygen species and secrete proinflammatory cytokines. RNA-sequencing analysis of LDAM revealed a transcriptional profile driven by innate inflammation that is 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 (GRN), are causes of autosomal-dominant forms of human neurodegenerative diseases. We therefore propose that LDAM contribute to age-related and genetic forms of neurodegeneration.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Aging / Microglia / Lipids Limits: Animals / Humans Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2020 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Aging / Microglia / Lipids Limits: Animals / Humans Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2020 Document type: Article Affiliation country: United States