Detection of Synaptic Proteins in Microglia by Flow Cytometry.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_49FE862930E6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Detection of Synaptic Proteins in Microglia by Flow Cytometry.
Journal
Frontiers in molecular neuroscience
Author(s)
Brioschi S., d'Errico P., Amann L.S., Janova H., Wojcik S.M., Meyer-Luehmann M., Rajendran L., Wieghofer P., Paolicelli R.C., Biber K.
ISSN
1662-5099 (Print)
ISSN-L
1662-5099
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
13
Pages
149
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
A growing body of evidence indicates that microglia actively remove synapses in vivo, thereby playing a key role in synaptic refinement and modulation of brain connectivity. This phenomenon was mainly investigated in immunofluorescence staining and confocal microscopy. However, a quantification of synaptic material in microglia using these techniques is extremely time-consuming and labor-intensive. To address this issue, we aimed to quantify synaptic proteins in microglia using flow cytometry. With this approach, we first showed that microglia from the healthy adult mouse brain contain a detectable level of VGLUT1 protein. Next, we found more than two-fold increased VGLUT1 immunoreactivity in microglia from the developing brain (P15) as compared to adult microglia. These data indicate that microglia-mediated synaptic pruning mostly occurs during the brain developmental period. We then quantified the VGLUT1 staining in microglia in two transgenic models characterized by pathological microglia-mediated synaptic pruning. In the 5xFAD mouse model of Alzheimer's disease (AD) microglia exhibited a significant increase in VGLUT1 immunoreactivity before the onset of amyloid pathology. Moreover, conditional deletion of TDP-43 in microglia, which causes a hyper-phagocytic phenotype associated with synaptic loss, also resulted in increased VGLUT1 immunoreactivity within microglia. This work provides a quantitative assessment of synaptic proteins in microglia, under homeostasis, and in mouse models of disease.
Keywords
5xFAD model, TDP-43 conditional knock-out, VGLUT1, microglia, synaptic pruning
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2020 9:18
Last modification date
30/04/2021 6:10
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