TREM2 is required for microglial instruction of astrocytic synaptic engulfment in neurodevelopment
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.
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TREM2 is required for microglia to limit astrocyte synaptic engulfment during development.
“a recent study demonstrated that TREM2 is required for microglia to limit astrocyte synaptic engulfment during development [49].”
From TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo (2023) · cites this paper as [49]
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“Supporting this last point, a recent study demonstrated that TREM2 is required for microglia to limit astrocyte synaptic engulfment during development [49].”
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- Authors
- Jay, T. R., von Saucken, V. E., Muñoz, B., Codocedo, J. F., Atwood, B. K., Lamb, B. T., & Landreth, G. E.
- Affiliations
- Case Western Reserve University (US)
- Department of Neurosciences Case Western Reserve University Cleveland Ohio
- Indiana University Indianapolis (US)
- Indiana University School of Medicine (US)
- Corresponding author
- Landreth, Gary E.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2019-07-02
- Volume
- 67
- Issue
- 10
- Pages
- 1873-1892
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2954780728
- Cited by
- 97
- References
- 26
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 15 · 2023: 10 · 2022: 11 · 2021: 16 · 2020: 18 · 2019: 2
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Author eBooks
- Funders
- Alzheimer's Association (BFG‐15‐364590)
- National Institute on Aging (F31 AG048704, R01 AG050597, RF1 AG051495)
- National Institute on Alcohol Abuse and Alcoholism (R00 AA023507)
- National Institutes of Health (S10‐OD024981)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- TREM2, microglia, astrocytes, synaptic engulfment, synaptic pruning, brain development, synapse number, TREM2 knockout mice, high-fat diet, synaptic loss, neurodegeneration, brain injury
- MeSH terms
- Animals, Astrocytes, Brain, Female, Male, Membrane Glycoproteins, Random Allocation, Receptors, Immunologic, Synapses, Microglia, Mice, Knockout, Tissue Culture Techniques, Diet, High-Fat
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