Evidence map›Paper›PMID 35354026›Full record

ArticleCell reports2022

Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses.

Jessica L Bolton, Annabel K Short, Shivashankar Othy, Cassandra L Kooiker, Manlin Shao, Benjamin G Gunn, Jaclyn Beck, Xinglong Bai, Stephanie M Law, Julie C Savage and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
11.4field-weighted citation impact, top 1% of its field
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

103 citing papers in PubMed, 146 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Disrupted maternal care alters neural-microglia interactions in the primate paralaminar (PL) nucleus of the amygdala.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  9. Immunity in Rodent Models of Stress.Biological psychiatry · 2026
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Microglia as critical mediators linking perinatal immune stress to mental health trajectories.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 3 countries.

Jessica L BoltonDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA. Electronic address: jbolton@gsu.edu.
Annabel K ShortDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA.
Shivashankar OthyDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Cassandra L KooikerDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA.
Manlin ShaoDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA.
Benjamin G GunnDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA; Division of Neuroscience, Medical Research Institute, Dundee University, Ninewells Hospital and Medical School, Dundee, UK.
Jaclyn BeckDepartment of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA.
Xinglong BaiDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA.
Stephanie M LawDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA.
Julie C SavageDépartement de Médecine Moléculaire, Université Laval, Québec City, QC, Canada; Axe Neurosciences, Centre de recherche du CHU de Québec, Québec City, QC, Canada.
Jeremy J LambertDivision of Neuroscience, Medical Research Institute, Dundee University, Ninewells Hospital and Medical School, Dundee, UK.
Delia BelelliDivision of Neuroscience, Medical Research Institute, Dundee University, Ninewells Hospital and Medical School, Dundee, UK.
Marie-Ève TremblayDépartement de Médecine Moléculaire, Université Laval, Québec City, QC, Canada; Axe Neurosciences, Centre de recherche du CHU de Québec, Québec City, QC, Canada.
Michael D CahalanDepartment of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Tallie Z BaramDepartment of Pediatrics, University of California, Irvine, Irvine, CA, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA, USA; Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA. Electronic address: tallie@uci.edu.
University of California, Irvine · USCentre hospitalier universitaire de Québec · CANinewells Hospital · GB

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Structural & Network-Function Correlates of Fragmented Early-Life Across SpeciesP50MH096889 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI BARAM, TALLIE Z. · 2013 to 2023
$25.4M
Uncover Strategies Used By Biological SystemsP50GM076516 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI NIE, QING · 2007 to 2016
$25.1M
Molecular Mechanisms of lon Channels in T LymphocytesR01NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 1985 to 2022
$7.0M
Effects of Early-Life Experience: Role of CRHR01MH073136 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI BARAM, TALLIE Z. · 2005 to 2020
$4.6M
Cellular and Molecular Mechanisms of Regulatory T Cells in EAER01AI121945 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 2016 to 2020
$2.5M
Defining the Role of Microglia in the Synaptic Rewiring of the Hypothalamus by Early life AdversityR00MH120327 · NIMH · GEORGIA STATE UNIVERSITY · PI BOLTON, JESSICA LYNN · 2021 to 2023
$747k
The thalamic paraventricular nucleus mediates the influence of early-life adversity on reward-seeking behaviorsF30MH126615 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI KOOIKER, CASSANDRA LEIGH · 2021 to 2025
$192k
Defining the Role of Microglia in the Synaptic Rewiring of the Hypothalamus by Early life AdversityK99MH120327 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI BOLTON, JESSICA LYNN · 2019 to 2020
$180k
NCI NIH HHS P30 CA062203NIAID NIH HHS R01 AI121945NIGMS NIH HHS P50 GM076516NIMH NIH HHS F30 MH126615NIMH NIH HHS K99 MH120327NIMH NIH HHS P50 MH096889NIMH NIH HHS R00 MH120327NIMH NIH HHS R01 MH073136NINDS NIH HHS R01 NS014609
6 · The paper itself

Abstract

Several mental illnesses, characterized by aberrant stress reactivity, often arise after early-life adversity (ELA). However, it is unclear how ELA affects stress-related brain circuit maturation, provoking these enduring vulnerabilities. We find that ELA increases functional excitatory synapses onto stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons, resulting from disrupted developmental synapse pruning by adjacent microglia. Microglial process dynamics and synaptic element engulfment were attenuated in ELA mice, associated with deficient signaling of the microglial phagocytic receptor MerTK. Accordingly, selective chronic chemogenetic activation of ELA microglia increased microglial process dynamics and reduced excitatory synapse density to control levels. Notably, selective early-life activation of ELA microglia normalized adult acute and chronic stress responses, including stress-induced hormone secretion and behavioral threat responses, as well as chronic adrenal hypertrophy of ELA mice. Thus, microglial actions during development are powerful contributors to mechanisms by which ELA sculpts the connectivity of stress-regulating neurons, promoting vulnerability to stress and stress-related mental illnesses.

Indexed as

Corticotropin-Releasing HormoneNeural Stem CellsAnimalsMiceMicrogliaNeuronsSynapsesCorticotropin-Releasing Hormone2-photon imagingchemogeneticscorticotropin-releasing factorCP: NeuroscienceMerTKmicrogliaprocess dynamicsstresssynaptic pruning

Identifiers

PMID35354026
PMCPMC9014810
OpenAlexW4220936272

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.