TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment

Taylor R. Jay, Victoria E. von Saucken, Braulio Muñoz, Juan F. Codocedo, Brady K. Atwood, Bruce Lamb, Gary E. Landreth

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalGlia
DOIs
StatePublished - Jan 1 2019

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Microglia
Synapses
Astrocytes
Neuronal Plasticity
Brain Diseases
High Fat Diet
Neurodegenerative Diseases
Brain Injuries
Hippocampus

Keywords

  • astrocyte
  • glia
  • microglia
  • pruning

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Jay, T. R., von Saucken, V. E., Muñoz, B., Codocedo, J. F., Atwood, B. K., Lamb, B., & Landreth, G. E. (2019). TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment. Glia. https://doi.org/10.1002/glia.23664

TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment. / Jay, Taylor R.; von Saucken, Victoria E.; Muñoz, Braulio; Codocedo, Juan F.; Atwood, Brady K.; Lamb, Bruce; Landreth, Gary E.

In: Glia, 01.01.2019.

Research output: Contribution to journalArticle

Jay, Taylor R. ; von Saucken, Victoria E. ; Muñoz, Braulio ; Codocedo, Juan F. ; Atwood, Brady K. ; Lamb, Bruce ; Landreth, Gary E. / TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment. In: Glia. 2019.
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