Clearance of β-amyloid and synapses by the optogenetic depolarization of microglia is complement selective.

Details

Serval ID
serval:BIB_C8B526B701E9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clearance of β-amyloid and synapses by the optogenetic depolarization of microglia is complement selective.
Journal
Neuron
Author(s)
Lv Z., Chen L., Chen P., Peng H., Rong Y., Hong W., Zhou Q., Li N., Li B., Paolicelli R.C., Zhan Y.
ISSN
1097-4199 (Electronic)
ISSN-L
0896-6273
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Microglia actively monitor the neighboring brain microenvironments and constantly contact synapses with their unique ramified processes. In neurodegenerative diseases, including Alzheimer's disease (AD), microglia undergo morphological and functional alterations. Whether the direct manipulation of microglia can selectively or concurrently modulate synaptic function and the response to disease-associated factors remains elusive. Here, we employ optogenetic methods to stimulate microglia in vitro and in vivo. Membrane depolarization rapidly changes microglia morphology and leads to enhanced phagocytosis. We found that the optogenetic stimulation of microglia can efficiently promote β-amyloid (Aβ) clearance in the brain parenchyma, but it can also enhance synapse elimination. Importantly, the inhibition of C1q selectively prevents synapse loss induced by microglia depolarization but does not affect Aβ clearance. Our data reveal independent microglia-mediated phagocytosis pathways toward Aβ and synapses. Our results also shed light on a synergistic strategy of depolarizing microglia and inhibiting complement functions for the clearance of Aβ while sparing synapses.
Keywords
Ad, Alzheimer's disease, amyloid, complement, depolarization, microglia, optogenetics, phygocytosis, synapse elimination, AD
Pubmed
Create date
01/02/2024 16:34
Last modification date
02/02/2024 7:32
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