Evidence map›Paper›PMID 27698409›Full record

ArticleScientific reports2016

Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele.

Eileen N Oni, Apoorva Halikere, Guohui Li, Alana J Toro-Ramos, Mavis R Swerdel, Jessica L Verpeut, Jennifer C Moore, Nicholas T Bello, Laura J Bierut, Alison Goate and 3 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. 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
2.4field-weighted citation impact, top 11% 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, 38 citations in OpenAlex.

  1. Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020
    Pooled it
  2. Article
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  10. Whole Cell Patch Clamp Electrophysiology in Human Neuronal Cells.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  11. Article
  12. Optimized splitting of mixed-species RNA sequencing data.Journal of bioinformatics and computational biology · 2022
    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

13 authors at 3 institutions in 1 country.

Eileen N OniCell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
Apoorva HalikereChild Health Institute of New Jersey &Dept. of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Guohui LiChild Health Institute of New Jersey &Dept. of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Alana J Toro-RamosCell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
Mavis R SwerdelCell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
Jessica L VerpeutDepartment of Animal Sciences, Rutgers University, New Brunswick, NJ, USA.
Jennifer C MooreHuman Genetics Institute of New Jersey, Rutgers University and RWJMS, Piscataway, NJ, USA.
Nicholas T BelloDepartment of Animal Sciences, Rutgers University, New Brunswick, NJ, USA.
Laura J BierutDepartment of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Alison GoateNeuroscience Department, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jay A TischfieldHuman Genetics Institute of New Jersey, Rutgers University and RWJMS, Piscataway, NJ, USA.
Zhiping P PangChild Health Institute of New Jersey &Dept. of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Ronald P HartCell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
Rutgers, The State University of New Jersey · USIcahn School of Medicine at Mount Sinai · USWashington University in St. Louis · US

Funding

NIMH Center Repository Supporting Stem Cell ResearchU24MH068457 · NIMH · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI BRZUSTOWICZ, LINDA M, KNOWLES, JAMES A · 2003 to 2024
$213.8M
Subject CollectionU10AA008401 · NIAAA · SUNY DOWNSTATE MEDICAL CENTER · PI BERNICE PORJESZ · 1989 to 2026
$162.7M
UMDNJ-RUTGERS UNIVERSITY PIPELINE PROGRAMR25GM055145 · NIGMS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI HAIMOVICH, BEATRICE, LANGER, JEROME ALAN · 1996 to 2020
$8.7M
Deciphering the neural basis of alcohol use disorders using human and mouse neuronsR01AA023797 · NIAAA · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI ZHIPING P. PANG · 2016 to 2026
$4.8M
Phenotypic analysis of human iPSC carrying addiction-associated gene variantsR21DA032984 · NIDA · RUTGERS, THE STATE UNIV OF N.J. · PI HART, RONALD P, TISCHFIELD, JAY ARNOLD · 2011 to 2012
$425k
Developing an In Vitro Neurocircuitry Model of Addiction using Risk-Associated HuR21DA035594 · NIDA · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI HART, RONALD P, PANG, ZHIPING P. · 2013 to 2014
$409k
Neuronal basis of OPRM1 A118G polymorphism in alcohol use disordersF31AA024033 · NIAAA · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI HALIKERE, APOORVA · 2015 to 2017
$93k
NIAAA NIH HHS F31 AA024033NIAAA NIH HHS R01 AA023797NIAAA NIH HHS U10 AA008401NIDA NIH HHS R21 DA032984NIDA NIH HHS R21 DA035594NIGMS NIH HHS R25 GM055145NIMH NIH HHS U24 MH068457
6 · The paper itself

Abstract

Genetic variation in nicotinic receptor alpha 5 (CHRNA5) has been associated with increased risk of addiction-associated phenotypes in humans yet little is known the underlying neural basis. Induced pluripotent stem cells (iPSCs) were derived from donors homozygous for either the major (D398) or the minor (N398) allele of the nonsynonymous single nucleotide polymorphism (SNP), rs16969968, in CHRNA5. To understand the impact of these nicotinic receptor variants in humans, we differentiated these iPSCs to dopamine (DA) or glutamatergic neurons and then tested their functional properties and response to nicotine. Results show that N398 variant human DA neurons differentially express genes associated with ligand receptor interaction and synaptic function. While both variants exhibited physiological properties consistent with mature neuronal function, the N398 neuronal population responded more actively with an increased excitatory postsynaptic current response upon the application of nicotine in both DA and glutamatergic neurons. Glutamatergic N398 neurons responded to lower nicotine doses (0.1 μM) with greater frequency and amplitude but they also exhibited rapid desensitization, consistent with previous analyses of N398-associated nicotinic receptor function. This study offers a proof-of-principle for utilizing human neurons to study gene variants contribution to addiction.

Indexed as

AllelesCells, CulturedGene Expression ProfilingGenetic VariationGlutamic AcidHumansInduced Pluripotent Stem CellsNerve Tissue ProteinsNeuronsNicotineReceptors, NicotinicCHRNA5 protein, humanGlutamic AcidNerve Tissue ProteinsNicotineReceptors, Nicotinic

Identifiers

PMID27698409
PMCPMC5048107
OpenAlexW2527699779

What OpenQuestion holds

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Registered trials

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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.