Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain.

Autor: Shahidehpour RK; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA; Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Higdon RE; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA; Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Crawford NG; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA; Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Neltner JH; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA., Ighodaro ET; Department of Neuroscience, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Patel E; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Price D; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA., Nelson PT; Department of Neuroscience, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Pathology and Laboratory Medicine, Division of Neuropathology, University of Kentucky, Lexington, KY, USA., Bachstetter AD; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA; Department of Neuroscience, University of Kentucky, Lexington, KY, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. Electronic address: adam.bachstetter@uky.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2021 Mar; Vol. 99, pp. 19-27. Date of Electronic Publication: 2021 Jan 07.
DOI: 10.1016/j.neurobiolaging.2020.12.003
Abstrakt: Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared with controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy. These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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