Evidence map›Paper›PMID 30007309›Full record

ArticleBrain : a journal of neurology2018

Motor neuron-derived microRNAs cause astrocyte dysfunction in amyotrophic lateral sclerosis.

Mariah L Hoye, Melissa R Regan, Leah A Jensen, Allison M Lake, Linga V Reddy, Svetlana Vidensky, Jean-Philippe Richard, Nicholas J Maragakis, Jeffrey D Rothstein, Joseph D Dougherty and 1 more

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

Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Mariah L HoyeDepartment of Neurology, Washington University School of Medicine; St. Louis, MO, USA.
Melissa R ReganDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Leah A JensenDepartment of Neurology, Washington University School of Medicine; St. Louis, MO, USA.
Allison M LakeDepartment of Genetics, Washington University School of Medicine; St. Louis, MO, USA.
Linga V ReddyDepartment of Neurology, Washington University School of Medicine; St. Louis, MO, USA.
Svetlana VidenskyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jean-Philippe RichardDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nicholas J MaragakisDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeffrey D RothsteinDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joseph D DoughertyDepartment of Genetics, Washington University School of Medicine; St. Louis, MO, USA.
Timothy M MillerDepartment of Neurology, Washington University School of Medicine; St. Louis, MO, USA.
Johns Hopkins University · USWashington University in St. Louis · USUniversity of Missouri–St. Louis · US

Funding

Using motor neuron specific miRNA to understand and develop novel therapeutics for motor neuron diseaseR01NS078398 · NINDS · WASHINGTON UNIVERSITY · PI MILLER, TIMOTHY M. · 2012 to 2021
$3.9M
Regulation of local translation in gliaR01NS102272 · NINDS · WASHINGTON UNIVERSITY · PI JOSEPH D DOUGHERTY · 2017 to 2026
$3.8M
SHORT-TERM TRAINING STUDENTS IN HEALTH PROFESSIONAL SCHOT35HL007815 · NHLBI · WASHINGTON UNIVERSITY · PI CHUNG, KOONG-NAH · 1995 to 2020
$2.8M
Expanding Access to Planar Illumination Microscopy in a Neuroimaging CoreR24NS086741 · NINDS · WASHINGTON UNIVERSITY · PI TAGHERT, PAUL H · 2014 to 2017
$814k
Changing tau Protein Levels and tau Protein Isoforms in Mouse Models of DementiaK08NS074194 · NINDS · WASHINGTON UNIVERSITY · PI MILLER, TIMOTHY M. · 2010 to 2012
$548k
Defining Motor Neuron-Specific miRNAs in ALSF31NS092340 · NINDS · WASHINGTON UNIVERSITY · PI HOYE, MARIAH LAWLER · 2015 to 2017
$90k
NHLBI NIH HHS T35 HL007815NINDS NIH HHS F31 NS092340NINDS NIH HHS K08 NS074194NINDS NIH HHS R01 NS078398NINDS NIH HHS R01 NS102272NINDS NIH HHS R24 NS086741
6 · The paper itself

Abstract

We recently demonstrated that microRNA-218 (miR-218) is greatly enriched in motor neurons and is released extracellularly in amyotrophic lateral sclerosis model rats. To determine if the released, motor neuron-derived miR-218 may have a functional role in amyotrophic lateral sclerosis, we examined the effect of miR-218 on neighbouring astrocytes. Surprisingly, we found that extracellular, motor neuron-derived miR-218 can be taken up by astrocytes and is sufficient to downregulate an important glutamate transporter in astrocytes [excitatory amino acid transporter 2 (EAAT2)]. The effect of miR-218 on astrocytes extends beyond EAAT2 since miR-218 binding sites are enriched in mRNAs translationally downregulated in amyotrophic lateral sclerosis astrocytes. Inhibiting miR-218 with antisense oligonucleotides in amyotrophic lateral sclerosis model mice mitigates the loss of EAAT2 and other miR-218-mediated changes, providing an important in vivo demonstration of the relevance of microRNA-mediated communication between neurons and astrocytes. These data define a novel mechanism in neurodegeneration whereby microRNAs derived from dying neurons can directly modify the glial phenotype and cause astrocyte dysfunction.

Indexed as

Amino Acid Transport System X-AGAmyotrophic Lateral SclerosisAnimalsAstrocytesCells, CulturedDisease Models, AnimalDown-RegulationExcitatory Amino Acid Transporter 2Glutamic AcidHEK293 CellsHumansMiceMice, Inbred C57BLMicroRNAsMotor NeuronsNeurogliaAmino Acid Transport System X-AGExcitatory Amino Acid Transporter 2Glutamic AcidMicroRNAsMIRN218 microRNA, humanMIRN218 microRNA, mouse

Identifiers

PMID30007309
PMCPMC6113638
OpenAlexW2865680083

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.