Evidence map›Paper›PMID 25559931›Full record

ArticleNeuroscience2015

Altered iPSC-derived neurons' sodium channel properties in subjects with Monge's disease.

H W Zhao, X Q Gu, T Chailangkarn, G Perkins, D Callacondo, O Appenzeller, O Poulsen, D Zhou, A R Muotri, G G Haddad

Open access · bronzeAbstract read
In one paragraph

Article in Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  9. The NaNeuroscience · 2016
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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

10 authors at 4 institutions in 2 countries.

H W ZhaoDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
X Q GuDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
T ChailangkarnDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
G PerkinsNational Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, CA, USA.
D CallacondoLaboratorios de Investigación y Desarrollo, Universidad Peruana Cayetano Heredia, Lima 36, Peru.
O AppenzellerNew Mexico Health Enhancement and Marathon Clinics Research Foundation, Albuquerque, NM 87122, USA.
O PoulsenDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
D ZhouDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
A R MuotriDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA; The Rady Children's Hospital, San Diego, CA 92123, USA.
G G HaddadDepartment of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA; The Rady Children's Hospital, San Diego, CA 92123, USA. Electronic address: ghaddad@ucsd.edu.
University of California, San Diego · USMarathon Oil (United States) · USRady Children's Hospital-San Diego · USUniversidad Peruana Cayetano Heredia · PE

Funding

IVEM and Image Analysis ResourceP41GM103412 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ELLISMAN, MARK H · 2012 to 2019
$17.9M
Systems Biology CoreP01HL098053 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI POWELL, FRANK L. · 2010 to 2014
$10.2M
Modeling autism with human pluripotent cellsDP2OD006495 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2009 to 2009
$2.3M
NHLBI NIH HHS 5P01HL098053NHLBI NIH HHS P01 HL098053NIGMS NIH HHS P41 GM103412NIH HHS 1-DP2-OD006495-01NIH HHS DP2 OD006495
6 · The paper itself

Abstract

Monge's disease, also known as chronic mountain sickness (CMS), is a disease that potentially threatens more than 140 million highlanders during extended time living at high altitudes (over 2500m). The prevalence of CMS in Andeans is about 15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy at high altitudes; however, CMS subjects experience severe hypoxemia, erythrocytosis and many neurologic manifestations including migraine, headache, mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS neuropathology are not well understood and no ideal treatment is available to prevent or cure CMS, except for phlebotomy. In the current study, we reprogrammed fibroblast cells from both CMS and non-CMS subjects' skin biopsies into the induced pluripotent stem cells (iPSCs), then differentiated into neurons and compared their neuronal properties. We discovered that CMS neurons were much less excitable (higher rheobase) than non-CMS neurons. This decreased excitability was not caused by differences in passive neuronal properties, but instead by a significantly lowered Na(+) channel current density and by a shift of the voltage-conductance curve in the depolarization direction. Our findings provide, for the first time, evidence of a neuronal abnormality in CMS subjects as compared to non-CMS subjects, hoping that such studies can pave the way to a better understanding of the neuropathology in CMS.

Indexed as

Action PotentialsAdultAltitude SicknessCell Culture TechniquesCells, CulturedChronic DiseaseFibroblastsHumansImmunohistochemistryInduced Pluripotent Stem CellsMaleNeural Stem CellsNeurogenesisNeuronsPatch-Clamp TechniquesPeruSodium Channelschronic mountain sicknessinduced pluripotent stem cellsNa(+) channelneurons

Identifiers

PMID25559931
PMCPMC4323892
OpenAlexW2095223542

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.