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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Nature Portfolio
2023-11-01
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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. |
first_indexed | 2024-03-11T12:39:43Z |
format | Article |
id | doaj.art-808ca7f8840f426781d6f6718d971338 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-11T12:39:43Z |
publishDate | 2023-11-01 |
publisher | Nature Portfolio |
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series | Nature Communications |
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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