Evidence map›Paper›PMID 26847266›Full record

ArticleGlia2016

Dark microglia: A new phenotype predominantly associated with pathological states.

Kanchan Bisht, Kaushik P Sharma, Cynthia Lecours, Maria Gabriela Sánchez, Hassan El Hajj, Giampaolo Milior, Adrián Olmos-Alonso, Diego Gómez-Nicola, Giamal Luheshi, Luc Vallières and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Glia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 247 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
247citing papers in PubMed, 1 pooled it
20.0field-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

247 citing papers in PubMed, 1 synthesis or guideline pooled it, 428 citations in OpenAlex.

  1. Pooled it
  2. Glial cells in neuropathic pain.Physiological reviews · 2026
    Review
  3. TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Implications of Mucin-TypeMolecules (Basel, Switzerland) · 2025
    Review

187 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 7 institutions in 4 countries.

Kanchan BishtAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Kaushik P SharmaAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Cynthia LecoursAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Maria Gabriela SánchezAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Hassan El HajjAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Giampaolo MiliorDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
Adrián Olmos-AlonsoCentre for Biological Sciences, University of Southampton, Southampton, United Kingdom.
Diego Gómez-NicolaCentre for Biological Sciences, University of Southampton, Southampton, United Kingdom.
Giamal LuheshiDouglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Québec, Canada.
Luc VallièresAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Igor BranchiSection of Behavioural Neurosciences, Department of Cell Biology and Neurosciences, Istituto Superiore Di Sanità, Rome, Italy.
Laura MaggiDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
Cristina LimatolaDepartment of Physiology and Pharmacology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
Oleg ButovskyAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Marie-Ève TremblayAxe Neurosciences, Centre De Recherche Du CHU De Québec, Québec, Québec, Canada.
Centre hospitalier universitaire de Québec · CAIstituto Pasteur · ITUniversity of Southampton · GBDouglas Mental Health University Institute · CAHarvard University · USIstituto Superiore di Sanità · ITSapienza University of Rome · IT

Funding

Targeting TGFb/IFNy-IRF8 Signaling to Modulate Monocytes and their Crosstalk with Microglia and Astrocytes to Treat Multiple SclerosisR01NS088137 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Oleg Butovsky · 2014 to 2026
$4.9M
Medical Research Council MR/K022687/1NINDS NIH HHS R01 NS088137
6 · The paper itself

Abstract

The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading to propose new pathogenic mechanisms. To study microglial implication in the loss of synapses, the best pathological correlate of cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered the existence of a new microglial phenotype that is rarely present under steady state conditions, in hippocampus, cerebral cortex, amygdala, and hypothalamus, but becomes abundant during chronic stress, aging, fractalkine signaling deficiency (CX3 CR1 knockout mice), and Alzheimer's disease pathology (APP-PS1 mice). Even though these cells display ultrastructural features of microglia, they are strikingly distinct from the other phenotypes described so far at the ultrastructural level. They exhibit several signs of oxidative stress, including a condensed, electron-dense cytoplasm and nucleoplasm making them as "dark" as mitochondria, accompanied by a pronounced remodeling of their nuclear chromatin. Dark microglia appear to be much more active than the normal microglia, reaching for synaptic clefts, while extensively encircling axon terminals and dendritic spines with their highly ramified and thin processes. They stain for the myeloid cell markers IBA1 and GFP (in CX3 CR1-GFP mice), and strongly express CD11b and microglia-specific 4D4 in their processes encircling synaptic elements, and TREM2 when they associate with amyloid plaques. Overall, these findings suggest that dark microglia, a new phenotype that we identified based on their unique properties, could play a significant role in the pathological remodeling of neuronal circuits, especially at synapses.

Indexed as

AgingAldehyde DehydrogenaseAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsAntigens, CDCerebral CortexCX3C Chemokine Receptor 1Disease Models, AnimalFormyltetrahydrofolate DehydrogenaseGreen Fluorescent ProteinsMiceMice, Inbred C57BLMice, TransgenicMicrogliaNerve Tissue ProteinsAldehyde DehydrogenaseAmyloid beta-Protein PrecursorAntigens, CDCX3C Chemokine Receptor 1Cx3cr1 protein, mouseFormyltetrahydrofolate DehydrogenaseGreen Fluorescent ProteinsNerve Tissue ProteinsOxidoreductases Acting on CH-NH Group DonorsPresenilin-1Receptors, Chemokineagingmicroglianeurodegenerative diseasesstresssynapses

Identifiers

PMID26847266
PMCPMC4949554
OpenAlexW2256955303

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.