Evidence map›Paper›PMID 31029597›Full record

ArticleExperimental neurology2019

Concentration-dependent effects of CSF1R inhibitors on oligodendrocyte progenitor cells ex vivo and in vivo.

Yiting Liu, Katherine S Given, Erin L Dickson, Gregory P Owens, Wendy B Macklin, Jeffrey L Bennett

Open access · greenAbstract read
In one paragraph

Article in Experimental neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

59 citing papers in PubMed, 115 citations in OpenAlex.

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  6. Neonatal microglia replacement in mice modulates seizure severity in adulthood.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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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

6 authors at 1 institution in 1 country.

Yiting LiuDepartment of Neurology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: Yiting.liu@ucdenver.edu.
Katherine S GivenDepartment of Cell & Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.
Erin L DicksonDepartment of Cell & Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.
Gregory P OwensDepartment of Neurology, University of Colorado School of Medicine, Aurora, CO, USA.
Wendy B MacklinDepartment of Cell & Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA; Program in Neuroscience, University of Colorado School of Medicine, Aurora, CO, USA.
Jeffrey L BennettDepartment of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA; Program in Neuroscience, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: Jeffrey.bennett@ucdenver.edu.
University of Colorado Denver · US

Funding

Autoimmunity Center of Excellence Clinical Research ProgramUM1AI110498 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WOFSY, DAVID · 2014 to 2019
$31.4M
Humoral Immunity, Astrocyte Injury, and Demyelination in Neuromyelitis OpticaR01EY022936 · NEI · UNIVERSITY OF COLORADO DENVER · PI BENNETT, JEFFREY L · 2013 to 2022
$3.8M
MYFLIN PROTEIN GENE EXPRESSIONR01NS025304 · NINDS · UNIVERSITY OF COLORADO DENVER · PI MACKLIN, WENDY B · 1987 to 2013
$3.3M
The Role of Intrathecal Plasma Cell Clones in MS PathogenesisR01NS072141 · NINDS · UNIVERSITY OF COLORADO DENVER · PI OWENS, GREGORY PARKS · 2011 to 2015
$1.3M
NEI NIH HHS R01 EY022936NIAID NIH HHS UM1 AI110498NINDS NIH HHS R01 NS025304NINDS NIH HHS R01 NS072141
6 · The paper itself

Abstract

Microglia are the principal resident immune cells in the central nervous system (CNS) and play important roles in CNS development, maintenance and repair. The survival and development of microglia depends on colony-stimulating factor 1 receptor (CSF1R), a member of the platelet-derived growth factor receptor (PDGFR) family of tyrosine kinases. Recently pharmacological CSF1R inhibition has been used to investigate the effects of microglial depletion in numerous animal models of CNS disease. However, the effects of CSF1R inhibitors on other cell types in the CNS remains incompletely characterized. In this report, we compared the effect of two commonly used CSF1R inhibitors, PLX5622 and PLX3397, on microglia and oligodendrocyte progenitor cell (OPC) numbers. In ex vivo cerebellar slices and adult mouse brain, both PLX compounds caused robust microglia loss; the kinetics of microglial depletion was more rapid with PLX5622. While high-doses of PLX5622 and PLX3397 reduced OPC number in primary cultures in vitro and ex vivo, low-doses of PLX5622 did not affect the number of OPCs or mature oligodendroglia in culture or in vivo. In adult mice, treatment with PLX5622 had no effect on OPC numbers for 7 days; however, a mild reduction was observed after 21 days in some CNS regions. In contrast, PLX3397 caused significant OPC loss after 7 days of treatment, despite only modest microglia depletion. Neither PLX compound had a remarkable effect on mature oligodendrocytes or myelin protein expression following long-term oral administration. Our results show that CSF1R inhibition with PLX5622 can selectively deplete microglia ex vivo and in vivo without affecting OPC number, demonstrating that microglia are not essential for OPC viability in ex vivo slice cultures or adult CNS tissues.

Indexed as

AminopyridinesAnimalsBrainMiceMicrogliaOligodendrocyte Precursor CellsOrganic ChemicalsPyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorAminopyridinesCsf1r protein, mouseOrganic ChemicalspexidartinibPLX5622PyrrolesReceptors, Granulocyte-Macrophage Colony-Stimulating FactorCSF1R inhibitorsDepletionMicrogliaOligodendrocyte progenitor cells

Identifiers

PMID31029597
PMCPMC6615458
OpenAlexW2942223082

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.