Evidence map›Paper›PMID 40832299›Full record

ArticlebioRxiv : the preprint server for biology2025

The Microglial TREM2 Receptor Programs Hippocampal Development in a Mouse Model of Childhood Deprivation.

Sahabuddin Ahmed, Christian Bowers, Jose Munoz-Martin, Sumit Jamwal, Basavaraju G Sanganahalli, Lauryn Giuliano, Zoë A MacDowell Kaswan, Fahmeed Hyder, X William Yang, Arie Kaffman

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Sahabuddin AhmedDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.
Christian BowersDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.
Jose Munoz-MartinDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.
Sumit JamwalDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.
Basavaraju G SanganahalliDepartment of Radiology & Biomedical Imaging and Magnetic Resonance Research Center, Yale University, New Haven, CT, 06520, USA.
Lauryn GiulianoDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.
Zoë A MacDowell KaswanDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.
Fahmeed HyderDepartment of Radiology & Biomedical Imaging and Magnetic Resonance Research Center, Yale University, New Haven, CT, 06520, USA.
X William YangCenter for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0003-3705-7935
Arie KaffmanDepartment of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven CT, 06511, USA.

Funding

BAC Transgenic Mouse Models of TREM2 to Study Neuroprotective Mechanisms in ADRF1AG056114 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIANGDONG WILLIAM · 2017 to 2017
$4.1M
Dysregulation of the opioid system in early life adversityR01MH130825 · NIMH · YALE UNIVERSITY · PI Marcelo Dietrich, ARIE KAFFMAN · 2022 to 2026
$4.0M
Microglial TREM2 Mediates Hippocampal Synaptic and Cognitive Sequela of Early Deprivation and EnrichmentR01MH136490 · NIMH · YALE UNIVERSITY · PI ARIE KAFFMAN · 2024 to 2026
$2.1M
Role of microglial IRF8 in the developmental consequences of early adversityR01MH119164 · NIMH · YALE UNIVERSITY · PI KAFFMAN, ARIE · 2020 to 2024
$2.1M
NIA NIH HHS RF1 AG056114NIMH NIH HHS R01 MH119164NIMH NIH HHS R01 MH130825NIMH NIH HHS R01 MH136490
6 · The paper itself

Abstract

Childhood neglect and deprivation are the most common forms of adversity, yet their biological impact on cognitive development-and how enrichment mitigates these effects-remains unclear. Using limited bedding (LB) as a mouse model of deprivation, we previously showed that abnormal microglial-mediated synaptic pruning during the second and third postnatal weeks leads to impaired synaptic connectivity and hippocampal dysfunction, particularly in males. Here, we demonstrate that LB reduces expression of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in different mouse strains and that TREM2 deficiency contributes to, but does not fully explain, impaired microglial pruning. Overexpressing TREM2 restored microglial phagocytic function and rescued deficits in hippocampal connectivity and fear learning. Brief postnatal enrichment (P14-P17) also normalized synaptic pruning in a TREM2-dependent manner. Together, our findings identify TREM2 as a key molecular mediator of experience-dependent plasticity, revealing its central role in linking early-life deprivation and enrichment to cognitive outcomes later in life.

Indexed as

Early enrichmentEarly life adversityLimited beddingSynaptic pruningTREM2

Identifiers

PMID40832299
PMCPMC12363838

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.