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Differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain
- Source :
- eLife, Vol 9 (2020)
- Publication Year :
- 2020
- Publisher :
- eLife Sciences Publications Ltd, 2020.
-
Abstract
- To date, microglia subsets in the healthy CNS have not been identified. Utilizing autofluorescence (AF) as a discriminating parameter, we identified two novel microglia subsets in both mice and non-human primates, termed autofluorescence-positive (AF+) and negative (AF−). While their proportion remained constant throughout most adult life, the AF signal linearly and specifically increased in AF+ microglia with age and correlated with a commensurate increase in size and complexity of lysosomal storage bodies, as detected by transmission electron microscopy and LAMP1 levels. Post-depletion repopulation kinetics revealed AF− cells as likely precursors of AF+ microglia. At the molecular level, the proteome of AF+ microglia showed overrepresentation of endolysosomal, autophagic, catabolic, and mTOR-related proteins. Mimicking the effect of advanced aging, genetic disruption of lysosomal function accelerated the accumulation of storage bodies in AF+ cells and led to impaired microglia physiology and cell death, suggestive of a mechanistic convergence between aging and lysosomal storage disorders.
Details
- Language :
- English
- ISSN :
- 2050084X
- Volume :
- 9
- Database :
- Directory of Open Access Journals
- Journal :
- eLife
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2da604ca9b974a5299cfeca64a35662e
- Document Type :
- article
- Full Text :
- https://doi.org/10.7554/eLife.57495