Evidence map›Paper›PMID 25821842›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2015

P2Y12 expression and function in alternatively activated human microglia.

Craig S Moore, Ariel R Ase, Angham Kinsara, Vijayaraghava T S Rao, Mackenzie Michell-Robinson, Soo Yuen Leong, Oleg Butovsky, Samuel K Ludwin, Philippe Séguéla, Amit Bar-Or and 1 more

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

Article in Neurology(R) neuroimmunology & neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
15.4field-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

120 citing papers in PubMed, 1 synthesis or guideline pooled it, 243 citations in OpenAlex.

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  13. Astrocytic Ryk signaling coordinates scarring and wound healing after spinal cord injury.Proceedings of the National Academy of Sciences of the United States of America · 2025
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60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 2 countries.

Craig S MooreDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Ariel R AseDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Angham KinsaraDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Vijayaraghava T S RaoDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Mackenzie Michell-RobinsonDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Soo Yuen LeongDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Oleg ButovskyDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Samuel K LudwinDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Philippe SéguélaDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Amit Bar-OrDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Jack P AntelDivision of BioMedical Sciences (C.S.M.), Neuroscience, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland, Canada; Neuroimmunology Unit (C.S.M., A.A., A.K., V.T.S.R., M.M.-R., S.Y.L., P.S., A.B.-O., J.P.A.), Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; Center for Neurologic Diseases (O.B.), Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; and Department of Pathology and Molecular Medicine (S.K.L.), Queens University, Kingston, Ontario, Canada.
Brigham and Women's Hospital · USHarvard University · USMemorial University of Newfoundland · CA

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
NINDS NIH HHS R01 NS088137
6 · The paper itself

Abstract

objectiveTo investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation.

methodsWe performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain.

resultsWe demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium responses, which are blocked by selective P2Y12 antagonism. P2Y12 antagonism was also shown to decrease migratory and inflammatory responses in human microglia upon exposure to nucleotides that are released during CNS injury; no effects were observed in human monocytes or macrophages. In situ experiments confirm that P2Y12 is selectively expressed on human microglia and elevated under neuropathologic conditions that promote Th2 responses, such as parasitic CNS infection.

conclusionThese findings provide insight into the roles of M2 microglia in the context of neuroinflammation and suggest a mechanism to selectively target a functionally unique population of myeloid cells in the CNS.

Identifiers

PMID25821842
PMCPMC4370387
OpenAlexW2115825207

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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.