Title | TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Jay TR, von Saucken VE, Muñoz B, Codocedo JF, Atwood BK, Lamb BT, Landreth GE |
Journal | Glia |
Volume | 67 |
Issue | 10 |
Pagination | 1873-1892 |
Date Published | 2019 10 |
ISSN | 1098-1136 |
Abstract | 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. |
DOI | 10.1002/glia.23664 |
Alternate Journal | Glia |
PubMed ID | 31265185 |
Grant List | R01 AG050597 / AG / NIA NIH HHS / United States S10-OD024981 / NH / NIH HHS / United States RF1 AG051495 / AG / NIA NIH HHS / United States F31 AG048704 / AG / NIA NIH HHS / United States R00 AA023507 / AA / NIAAA NIH HHS / United States |
Submitted by bel2021 on December 2, 2019 - 10:08am