Evidence map›Paper›PMID 26565024›Full record

ArticleThe Journal of biological chemistry2016

Deletion of Monoglyceride Lipase in Astrocytes Attenuates Lipopolysaccharide-induced Neuroinflammation.

Gernot F Grabner, Thomas O Eichmann, Bernhard Wagner, Yuanqing Gao, Aitak Farzi, Ulrike Taschler, Franz P W Radner, Martina Schweiger, Achim Lass, Peter Holzer and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
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  10. Association ofCell journal · 2023
    Article
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  16. Article
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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

14 authors at 4 institutions in 3 countries.

Gernot F GrabnerFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Thomas O EichmannFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Bernhard Wagnerthe Institute of Biomedical Science, FH Joanneum University of Applied Sciences, 8020 Graz, Austria.
Yuanqing Gaothe Institute of Diabetes and Obesity, Helmholtz Center Munich, 85748 Garching, Germany.
Aitak Farzithe Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010 Graz, Austria, and.
Ulrike TaschlerFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Franz P W RadnerFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Martina SchweigerFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Achim LassFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
Peter Holzerthe Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010 Graz, Austria, and.
Erwin Zinserthe Institute of Biomedical Science, FH Joanneum University of Applied Sciences, 8020 Graz, Austria.
Matthias H Tschöpthe Institute of Diabetes and Obesity, Helmholtz Center Munich, 85748 Garching, Germany.
Chun-Xia Yithe Institute of Diabetes and Obesity, Helmholtz Center Munich, 85748 Garching, Germany, the Department of Endocrinology and Metabolism, Academic Medical Center Amsterdam, 1105 Amsterdam, The Netherlands.
Robert ZimmermannFrom the Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria, robert.zimmermann@uni-graz.at.
University of Graz · ATHelmholtz Zentrum München · DEFH JOANNEUM University of Applied Sciences · ATMedical University of Graz · AT

Funding

Austrian Science Fund FWF P 24294Austrian Science Fund FWF P 25193Austrian Science Fund FWF P 25944Austrian Science Fund FWF W 901
6 · The paper itself

Abstract

Monoglyceride lipase (MGL) is required for efficient hydrolysis of the endocannabinoid 2-arachidonoylglyerol (2-AG) in the brain generating arachidonic acid (AA) and glycerol. This metabolic function makes MGL an interesting target for the treatment of neuroinflammation, since 2-AG exhibits anti-inflammatory properties and AA is a precursor for pro-inflammatory prostaglandins. Astrocytes are an important source of AA and 2-AG, and highly express MGL. In the present study, we dissected the distinct contribution of MGL in astrocytes on brain 2-AG and AA metabolism by generating a mouse model with genetic deletion of MGL specifically in astrocytes (MKO(GFAP)). MKO(GFAP) mice exhibit moderately increased 2-AG and reduced AA levels in brain. Minor accumulation of 2-AG in the brain of MKO(GFAP) mice does not cause cannabinoid receptor desensitization as previously observed in mice globally lacking MGL. Importantly, MKO(GFAP) mice exhibit reduced brain prostaglandin E2 and pro-inflammatory cytokine levels upon peripheral lipopolysaccharide (LPS) administration. These observations indicate that MGL-mediated degradation of 2-AG in astrocytes provides AA for prostaglandin synthesis promoting LPS-induced neuroinflammation. The beneficial effect of astrocyte-specific MGL-deficiency is not fully abrogated by the inverse cannabinoid receptor 1 agonist SR141716 (Rimonabant) suggesting that the anti-inflammatory effects are rather caused by reduced prostaglandin synthesis than by activation of cannabinoid receptors. In conclusion, our data demonstrate that MGL in astrocytes is an important regulator of 2-AG levels, AA availability, and neuroinflammation.

Indexed as

Gene DeletionAnimalsArachidonic AcidsAstrocytesBehavior, AnimalBrainCytokinesEndocannabinoidsFemaleGlial Fibrillary Acidic ProteinGlyceridesInflammationLipopolysaccharidesMice, Inbred C57BLMice, KnockoutMicrogliaArachidonic AcidsCytokinesEndocannabinoidsGlial Fibrillary Acidic ProteinGlyceridesglyceryl 2-arachidonateLipopolysaccharidesMonoacylglycerol LipasesReceptor, Cannabinoid, CB1arachidonic acid (AA) (ARA)astrocyteendocannabinoidlipopolysaccharide (LPS)neuroinflammation

Identifiers

PMID26565024
PMCPMC4705409
OpenAlexW2178145614

What OpenQuestion holds

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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.