The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity.

Details

Serval ID
serval:BIB_0680EB4E5A11
Type
Article: article from journal or magazin.
Collection
Publications
Title
The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity.
Journal
Immunity
Author(s)
Filipello F., Morini R., Corradini I., Zerbi V., Canzi A., Michalski B., Erreni M., Markicevic M., Starvaggi-Cucuzza C., Otero K., Piccio L., Cignarella F., Perrucci F., Tamborini M., Genua M., Rajendran L., Menna E., Vetrano S., Fahnestock M., Paolicelli R.C., Matteoli M.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
15/05/2018
Peer-reviewed
Oui
Volume
48
Number
5
Pages
979-991.e8
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial innate immune receptor associated with a lethal form of early, progressive dementia, Nasu-Hakola disease, and with an increased risk of Alzheimer's disease. Microglial defects in phagocytosis of toxic aggregates or apoptotic membranes were proposed to be at the origin of the pathological processes in the presence of Trem2 inactivating mutations. Here, we show that TREM2 is essential for microglia-mediated synaptic refinement during the early stages of brain development. The absence of Trem2 resulted in impaired synapse elimination, accompanied by enhanced excitatory neurotransmission and reduced long-range functional connectivity. Trem2 <sup>-/-</sup> mice displayed repetitive behavior and altered sociability. TREM2 protein levels were also negatively correlated with the severity of symptoms in humans affected by autism. These data unveil the role of TREM2 in neuronal circuit sculpting and provide the evidence for the receptor's involvement in neurodevelopmental diseases.
Keywords
PSD95, TREM2, autism, development, microglia, synapse, synaptic pruning
Pubmed
Web of science
Create date
18/12/2018 10:57
Last modification date
20/08/2019 12:28
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