Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment

Abstract Engulfment of cellular material and proteins is a key function for microglia, a resident macrophage of the central nervous system (CNS). Among the techniques used to measure microglial engulfment, confocal light microscopy has been used the most extensively. Here, we show that autofluoresce...

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Main Authors: Jacob M. Stillman, Francisco Mendes Lopes, Jing-Ping Lin, Kevin Hu, Daniel S. Reich, Dorothy P. Schafer
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-42809-y
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author Jacob M. Stillman
Francisco Mendes Lopes
Jing-Ping Lin
Kevin Hu
Daniel S. Reich
Dorothy P. Schafer
author_facet Jacob M. Stillman
Francisco Mendes Lopes
Jing-Ping Lin
Kevin Hu
Daniel S. Reich
Dorothy P. Schafer
author_sort Jacob M. Stillman
collection DOAJ
description Abstract Engulfment of cellular material and proteins is a key function for microglia, a resident macrophage of the central nervous system (CNS). Among the techniques used to measure microglial engulfment, confocal light microscopy has been used the most extensively. Here, we show that autofluorescence (AF) likely due to lipofuscin (lipo-AF) and typically associated with aging, can also be detected within microglial lysosomes in the young mouse brain by light microscopy. This lipo-AF signal accumulates first within microglia and it occurs earliest in white versus gray matter. Importantly, in gray matter, lipo-AF signal can confound the interpretation of antibody-labeled synaptic material within microglia in young adult mice. We further show that there is an age-dependent accumulation of lipo-AF inside and outside of microglia, which is not affected by amyloid plaques. We finally implement a robust and cost-effective strategy to quench AF in mouse, marmoset, and human brain tissue.
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spelling doaj.art-808ca7f8840f426781d6f6718d9713382023-11-05T12:23:32ZengNature PortfolioNature Communications2041-17232023-11-0114111110.1038/s41467-023-42809-yLipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfmentJacob M. Stillman0Francisco Mendes Lopes1Jing-Ping Lin2Kevin Hu3Daniel S. Reich4Dorothy P. Schafer5Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical SchoolDepartment of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical SchoolTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of HealthDepartment of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical SchoolAbstract Engulfment of cellular material and proteins is a key function for microglia, a resident macrophage of the central nervous system (CNS). Among the techniques used to measure microglial engulfment, confocal light microscopy has been used the most extensively. Here, we show that autofluorescence (AF) likely due to lipofuscin (lipo-AF) and typically associated with aging, can also be detected within microglial lysosomes in the young mouse brain by light microscopy. This lipo-AF signal accumulates first within microglia and it occurs earliest in white versus gray matter. Importantly, in gray matter, lipo-AF signal can confound the interpretation of antibody-labeled synaptic material within microglia in young adult mice. We further show that there is an age-dependent accumulation of lipo-AF inside and outside of microglia, which is not affected by amyloid plaques. We finally implement a robust and cost-effective strategy to quench AF in mouse, marmoset, and human brain tissue.https://doi.org/10.1038/s41467-023-42809-y
spellingShingle Jacob M. Stillman
Francisco Mendes Lopes
Jing-Ping Lin
Kevin Hu
Daniel S. Reich
Dorothy P. Schafer
Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
Nature Communications
title Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
title_full Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
title_fullStr Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
title_full_unstemmed Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
title_short Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment
title_sort lipofuscin like autofluorescence within microglia and its impact on studying microglial engulfment
url https://doi.org/10.1038/s41467-023-42809-y
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