Evidence map›Paper›PMID 26134658›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015

miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction.

Maya E Woodbury, Robert W Freilich, Christopher J Cheng, Hirohide Asai, Seiko Ikezu, Jonathan D Boucher, Frank Slack, Tsuneya Ikezu

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. 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
6.7field-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, 94 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Maya E WoodburyDepartment of Pharmacology and Experimental Therapeutics and Graduate Program in Neuroscience, Boston University, Boston, Massachusetts 02118, and.ORCID http://orcid.org/0000-0003-0613-0220
Robert W FreilichDepartment of Pharmacology and Experimental Therapeutics and.
Christopher J ChengDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520.
Hirohide AsaiDepartment of Pharmacology and Experimental Therapeutics and.
Seiko IkezuDepartment of Pharmacology and Experimental Therapeutics and.
Jonathan D BoucherDepartment of Pharmacology and Experimental Therapeutics and.
Frank SlackDepartment of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520.
Tsuneya IkezuDepartment of Pharmacology and Experimental Therapeutics and Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, tikezu@bu.edu.ORCID http://orcid.org/0000-0002-3979-8596
Boston University · USYale University · US

Funding

Neuropathology CoreP30AG013846 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOWALL, NEIL W. · 1996 to 2020
$29.1M
TRAINING IN BIOMOLECULAR PHARMACOLOGYT32GM008541 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARB, DAVID H · 1997 to 2022
$5.2M
Anti-inflammatory regulation of beta-amyloidosisR21AG032600 · NIA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI IKEZU, TSUNEYA · 2009 to 2010
$346k
NIA NIH HHS 7R21AG032600NIA NIH HHS P30 AG013846NIA NIH HHS R21 AG032600NIGMS NIH HHS 5T32GM008541NIGMS NIH HHS T32 GM008541
6 · The paper itself

Abstract

Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development.

Indexed as

AnimalsCalcium-Binding ProteinsCell Culture TechniquesCell MovementCell ProliferationCoculture TechniquesDisease Models, AnimalDoxycyclineEmbryo, MammalianFemaleGene Expression RegulationGlial Fibrillary Acidic ProteinHippocampusInflammationInterleukin-6LipopolysaccharidesAif1 protein, mouseCalcium-Binding ProteinsDoxycyclineGlial Fibrillary Acidic ProteinInterleukin-6LipopolysaccharidesMicrofilament ProteinsMicroRNAsMirn155 microRNA, mouseNes protein, mouseNestinhippocampusmicrogliamicroRNAneurogenesisneuroinflammationtransgenic mice

Identifiers

PMID26134658
PMCPMC4571507
OpenAlexW1664596139

What OpenQuestion holds

Textmetadata
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.