Evidence map›Paper›PMID 31883839›Full record

ArticleImmunity2020

Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease.

Sebastian Werneburg, Jonathan Jung, Rejani B Kunjamma, Seung-Kwon Ha, Nicholas J Luciano, Cory M Willis, Guangping Gao, Natalia P Biscola, Leif A Havton, Stephen J Crocker and 3 more

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

Article in Immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers.

0numbers the graph read from it
0cells of the map it votes in
252citing papers in PubMed
19.2field-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

252 citing papers in PubMed, 438 citations in OpenAlex.

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  17. SV2A PET reveals synaptic density loss in experimental autoimmune encephalomyelitis and in a pilot multiple sclerosis study.Proceedings of the National Academy of Sciences of the United States of America · 2026
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192 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 7 institutions in 1 country.

Sebastian WerneburgDepartment of Neurobiology, Brudnik Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jonathan JungDepartment of Neurobiology, Brudnik Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Rejani B KunjammaDepartment of Neurology, University of Chicago, Chicago, IL 60637, USA.
Seung-Kwon HaTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Nicholas J LucianoTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Cory M WillisDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06032, USA.
Guangping GaoHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA 01605, USA; Department of Microbiologic and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Natalia P BiscolaDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Leif A HavtonDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Stephen J CrockerDepartment of Neuroscience, University of Connecticut School of Medicine, Farmington, CT 06032, USA.
Brian PopkoDepartment of Neurology, University of Chicago, Chicago, IL 60637, USA.
Daniel S ReichTranslational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Dorothy P SchaferDepartment of Neurobiology, Brudnik Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: dorothy.schafer@umassmed.edu.
University of Massachusetts Chan Medical School · USNational Institute of Neurological Disorders and Stroke · USUniversity of California, Los Angeles · USUniversity of Chicago · USUniversity of Connecticut · USNational Institutes of Health · USNeuropsychiatric Research Institute · US

Funding

Multimodal MRI in Multiple SclerosisZIANS003119 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI REICH, DANIEL · 2010 to 2025
$53.4M
Microglia-dependent mechanisms governing neural circuit plasticityR01MH113743 · NIMH · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Dorothy Patricia Schafer · 2017 to 2026
$4.9M
Regulation of CD4+ T cell-mediated Demyelination Following Oligo AblationR01NS099334 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MILLER, STEPHEN D, POPKO, BRIAN J · 2017 to 2021
$2.1M
Analysis of activity-dependent interactions between microglia and synapsesR00MH102351 · NIMH · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHAFER, DOROTHY PATRICIA · 2015 to 2017
$747k
Exploring Novel Activity-Dependent Mechanisms Regulating Microglia-Synapse InteractionsR21MH115353 · NIMH · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHAEFER, ANNE, SCHAFER, DOROTHY PATRICIA · 2017 to 2018
$480k
NIMH NIH HHS R00 MH102351NIMH NIH HHS R01 MH113743NIMH NIH HHS R21 MH115353NINDS NIH HHS R01 NS099334
6 · The paper itself

Abstract

Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. While work has focused on myelin and axon loss in MS, less is known about mechanisms underlying synaptic changes. Using postmortem human MS tissue, a preclinical nonhuman primate model of MS, and two rodent models of demyelinating disease, we investigated synapse changes in the visual system. Similar to other neurodegenerative diseases, microglial synaptic engulfment and profound synapse loss were observed. In mice, synapse loss occurred independently of local demyelination and neuronal degeneration but coincided with gliosis and increased complement component C3, but not C1q, at synapses. Viral overexpression of the complement inhibitor Crry at C3-bound synapses decreased microglial engulfment of synapses and protected visual function. These results indicate that microglia eliminate synapses through the alternative complement cascade in demyelinating disease and identify a strategy to prevent synapse loss that may be broadly applicable to other neurodegenerative diseases. VIDEO ABSTRACT.

Indexed as

AgedAged, 80 and overAnimalsCallithrixCell Line, TumorComplement C3Disease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalFemaleGliosisHumansMaleMiceMice, Inbred C57BLMicrogliaMiddle AgedComplement C3CR1L protein, humanReceptors, Complement 3bcomplementdemyelinationengulfmentgene therapymicrogliamultiple sclerosisneural-immuneneurodegenerationneuroinflammationsynapse

Identifiers

PMID31883839
PMCPMC6996144
OpenAlexW2996763848

What OpenQuestion holds

Textmetadata
LicenceTDM
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.