Evidence map›Paper›PMID 24686787›Full record

ArticleNature neuroscience2014

Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice.

Xiaoping Tong, Yan Ao, Guido C Faas, Sinifunanya E Nwaobi, Ji Xu, Martin D Haustein, Mark A Anderson, Istvan Mody, Michelle L Olsen, Michael V Sofroniew and 1 more

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

Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 363 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
363citing papers in PubMed, 1 pooled it
22.7field-weighted citation impact, top 1% 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

363 citing papers in PubMed, 1 synthesis or guideline pooled it, 586 citations in OpenAlex.

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303 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Xiaoping Tong1] Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. [2].
Yan Ao1] Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. [2].
Guido C FaasDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Sinifunanya E NwaobiDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Ji XuDepartment of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Martin D HausteinDepartment of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Mark A AndersonDepartment of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Istvan Mody1] Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. [2] Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Michelle L OlsenDepartment of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Michael V Sofroniew1] Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. [2].
Baljit S Khakh1] Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. [2] Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. [3].
University of California, Los Angeles · USUniversity of Alabama at Birmingham · US

Funding

Functions of astrocyte calcium signaling in the striatumR01NS060677 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KHAKH, BALJIT · 2008 to 2018
$4.3M
Astrocyte branchlet dysfunction as an early step in brain disordersDP1MH104069 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KHAKH, BALJIT · 2013 to 2017
$3.9M
Epigenetic Regulation of Kir4.1 and GLT1 in PathophysiologyR01NS075062 · NINDS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI OLSEN, MICHELLE L · 2013 to 2017
$1.6M
NIMH NIH HHS DP1 MH104069NIMH NIH HHS MH104069NINDS NIH HHS NS060677NINDS NIH HHS R01 NS060677NINDS NIH HHS R01 NS075062
6 · The paper itself

Abstract

Huntington's disease (HD) is characterized by striatal medium spiny neuron (MSN) dysfunction, but the underlying mechanisms remain unclear. We explored roles for astrocytes, in which mutant huntingtin is expressed in HD patients and mouse models. We found that symptom onset in R6/2 and Q175 HD mouse models was not associated with classical astrogliosis, but was associated with decreased Kir4.1 K(+) channel functional expression, leading to elevated in vivo striatal extracellular K(+), which increased MSN excitability in vitro. Viral delivery of Kir4.1 channels to striatal astrocytes restored Kir4.1 function, normalized extracellular K(+), ameliorated aspects of MSN dysfunction, prolonged survival and attenuated some motor phenotypes in R6/2 mice. These findings indicate that components of altered MSN excitability in HD may be caused by heretofore unknown disturbances of astrocyte-mediated K(+) homeostasis, revealing astrocytes and Kir4.1 channels as therapeutic targets.

Indexed as

Age FactorsAnimalsAstrocytesCorpus StriatumDisease Models, AnimalGreen Fluorescent ProteinsHEK293 CellsHindlimb SuspensionHumansHuntingtin ProteinHuntington DiseaseIn Vitro TechniquesKcnj10 ChannelLocomotionMiceMice, Inbred C57BLGreen Fluorescent ProteinsHtt protein, mouseHuntingtin ProteinKcnj10 ChannelNerve Tissue ProteinsNuclear ProteinsPotassium Channels, Inwardly Rectifying

Identifiers

PMID24686787
PMCPMC4064471
OpenAlexW2129082075

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.