학술논문

Microglia protect against age-associated brain pathologies.
Document Type
Academic Journal
Author
Munro DAD; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK. Electronic address: david.munro@ed.ac.uk.; Bestard-Cuche N; Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.; McQuaid C; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.; Chagnot A; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.; Shabestari SK; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.; Chadarevian JP; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.; Maheshwari U; Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Szymkowiak S; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.; Morris K; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK.; Mohammad M; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK.; Corsinotti A; Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.; Bradford B; The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, UK.; Mabbott N; The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, UK.; Lennen RJ; Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.; Jansen MA; Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.; Pridans C; Centre for Inflammation Research, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, UK.; McColl BW; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Discovery Brain Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.; Keller A; Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.; Blurton-Jones M; Department of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.; Montagne A; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.; Williams A; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK.; Priller J; UK Dementia Research Institute at the University of Edinburgh, Edinburgh Medical School, Chancellor's Building, Edinburgh EH16 4SB, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK; Department of Psychiatry and Psychotherapy, School of Medicine and Health, Klinikum rechts der Isar, Technical University Munich, and German Center for Mental Health (DZPG), 81675 Munich, Germany; Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité - Universitätsmedizin Berlin and DZNE, 10117 Berlin, Germany. Electronic address: josef.priller@ed.ac.uk.
Source
Publisher: Cell Press Country of Publication: United States NLM ID: 8809320 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-4199 (Electronic) Linking ISSN: 08966273 NLM ISO Abbreviation: Neuron Subsets: MEDLINE
Subject
Language
English
Abstract
Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the Csf1r ΔFIRE/ΔFIRE mouse model. In juvenile Csf1r ΔFIRE/ΔFIRE mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types. By contrast, with advancing age, pathologies accumulate in Csf1r ΔFIRE/ΔFIRE brains, macroglia become increasingly dysregulated, and white matter integrity declines, mimicking many pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly vulnerable to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular alterations, macroglial dysregulation, and severe tissue calcification. We show that populating Csf1r ΔFIRE/ΔFIRE brains with wild-type microglia protects against many of these pathological changes. Together with the accompanying study by Chadarevian and colleagues 1 , our results indicate that the lifelong absence of microglia results in an age-related neurodegenerative condition that can be counteracted via transplantation of healthy microglia.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024. Published by Elsevier Inc.)