Evidence map›Paper›PMID 32771067›Full record

ArticleActa neuropathologica communications2020

Microglia depletion diminishes key elements of the leukotriene pathway in the brain of Alzheimer's Disease mice.

J Michael, M S Unger, R Poupardin, P Schernthaner, H Mrowetz, J Attems, L Aigner

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

Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Arachidonic acid metabolism in spinal cord injury.Journal of advanced research · 2026
    Review
  4. Article
  5. Article
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  10. Review
  11. Receptors on Microglia.Advances in neurobiology · 2024
    Review
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  14. 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

7 authors at 2 institutions in 2 countries.

J MichaelInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.
M S UngerInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.
R PoupardinSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.
P SchernthanerInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.
H MrowetzInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria.
J AttemsInstitute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
L AignerInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. ludwig.aigner@pmu.ac.at.ORCID 0000-0002-1653-8046
Paracelsus Medical University · ATNewcastle University · GB

Funding

Austrian Science Fund FWF P 31362Medical Research Council G0400074Medical Research Council G0502157Medical Research Council G0900652
6 · The paper itself

Abstract

Leukotrienes (LTs) contribute to the neuropathology of chronic neurodegenerative disorders including Alzheimer's Disease (AD), where they mediate neuroinflammation and neuronal cell-death. In consequence, blocking the action of Leukotrienes (LTs) ameliorates pathologies and improves cognitive function in animal models of neurodegeneration. Surprisingly, the source of Leukotrienes (LTs) in the brain is largely unknown. Here, we identified the Leukotriene (LT) synthesis rate-limiting enzyme 5-Lipoxygenase (5-Lox) primarily in neurons and to a lesser extent in a subpopulation of microglia in human Alzheimer´s Disease (AD) hippocampus brain sections and in brains of APP Swedish PS1 dE9 (APP-PS1) mice, a transgenic model for Alzheimer´s Disease (AD) pathology. The 5-Lipoxygenase (5-Lox) activating protein (FLAP), which anchors 5-Lipoxygenase (5-Lox) to the membrane and mediates the contact to the substrate arachidonic acid, was confined exclusively to microglia with the entire microglia population expressing 5-Lipoxygenase activating protein (FLAP). To define the contribution of microglia in the Leukotriene (LT) biosynthesis pathway, we ablated microglia using the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in wildtype (WT) and APP-PS1 mice. Microglia ablation not only diminished the expression of FLAP and of the Leukotriene (LT) receptor Cysteinylleukotriene receptor 1 (CysLTR1), as expected based on their microglia cell type-specific expression, but also drastically reduced 5-Lipoxygenase (5-Lox) mRNA expression in the brain and its protein expression in neurons, in particular in wildtype (WT) mice. In conclusion i) microglia are key in Leukotriene (LT) biosynthesis, and ii) they regulate neuronal 5-Lipoxygenase (5-Lox) expression implying a yet unknown signaling mechanism between neurons and microglia.

Indexed as

5-Lipoxygenase-Activating ProteinsAlzheimer DiseaseAnimalsArachidonate 5-LipoxygenaseBrainFemaleHumansLeukotrienesMaleMiceMicrogliaNeurons5-Lipoxygenase-Activating ProteinsArachidonate 5-LipoxygenaseLeukotrienesAlzheimer’s diseaseCysteinyl-leukotrienesLeukotrienesMicrogliaRNAseq

Identifiers

PMID32771067
PMCPMC7414992
OpenAlexW3047843345

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.