Premium
TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment
Author(s) -
Jay Taylor R.,
Saucken Victoria E.,
Muñoz Braulio,
Codocedo Juan F.,
Atwood Brady K.,
Lamb Bruce T.,
Landreth Gary E.
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23664
Subject(s) - trem2 , microglia , synaptic pruning , neuroscience , synapse , biology , cx3cr1 , receptor , immunology , inflammation , chemokine receptor , chemokine , biochemistry
Variants in the microglial receptor TREM2 confer risk for multiple neurodegenerative diseases. However, it remains unknown how this receptor functions on microglia to modulate these diverse neuropathologies. To understand the role of TREM2 on microglia more generally, we investigated changes in microglial function in Trem2 −/− mice. We found that loss of TREM2 impairs normal neurodevelopment, resulting in reduced synapse number across the cortex and hippocampus in 1‐month‐old mice. This reduction in synapse number was not due directly to alterations in interactions between microglia and synapses. Rather, TREM2 was required for microglia to limit synaptic engulfment by astrocytes during development. While these changes were largely normalized later in adulthood, high fat diet administration was sufficient to reinitiate TREM2‐dependent modulation of synapse loss. Together, this identifies a novel role for microglia in instructing synaptic pruning by astrocytes to broadly regulate appropriate synaptic refinement, and suggests novel candidate mechanisms for how TREM2 and microglia could influence synaptic loss in brain injury and disease.