PMID- 29156239
OWN - NLM
STAT- MEDLINE
DCOM- 20180917
LR  - 20190201
IS  - 1873-6823 (Electronic)
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 66
DP  - 2018 Feb
TI  - Examining the effects of alcohol on GABA(A) receptor mRNA expression and function 
      in neural cultures generated from control and alcohol dependent donor induced 
      pluripotent stem cells.
PG  - 45-53
LID - S0741-8329(17)30713-9 [pii]
LID - 10.1016/j.alcohol.2017.08.005 [doi]
AB  - Factors influencing the development of alcohol-use disorder (AUD) are complex and 
      heterogeneous. While animal models have been crucial to identifying actions of 
      alcohol on neural cells, human-derived in vitro systems that reflect an 
      individual's genetic background hold promise in furthering our understanding of 
      the molecular and functional effects of alcohol exposure and the pathophysiology 
      of AUD. In this report, we utilized induced pluripotent stem cell (iPSCs)-derived 
      neural cell cultures obtained from healthy individuals (CTLs) and those with 
      alcohol dependence (ADs) to 1) examine the effect of 21-day alcohol exposure on 
      mRNA expression of three genes encoding GABA(A) receptor subunits (GABRA1, 
      GABRG2, and GABRD) using quantitative PCR, and 2) examine the effect of acute and 
      chronic alcohol exposure on GABA-evoked currents using whole-cell patch-clamp 
      electrophysiology. iPSCs from CTLs and ADs were differentiated into neural 
      cultures enriched for forebrain-type excitatory glutamate neurons. Following 
      21-day alcohol exposure, significant treatment effects were observed in GABRA1, 
      GABRG2, and GABRD mRNA expression. A modestly significant interaction between 
      treatment and donor phenotype was observed for GABRD, which was increased in cell 
      cultures derived from ADs. No effect of acute or chronic alcohol was observed on 
      GABA-evoked currents in neurons from either CTLs or ADs. This work extends 
      findings examining the effects of alcohol on the GABA(A) receptor in human cell 
      in vitro model systems.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Lieberman, Richard
AU  - Lieberman R
AD  - Alcohol Research Center, Department of Psychiatry, University of Connecticut 
      School of Medicine, Farmington, CT, 06030-1410, USA.
FAU - Kranzler, Henry R
AU  - Kranzler HR
AD  - Center for Studies of Addiction, Department of Psychiatry, Perelman School of 
      Medicine of the University of Pennsylvania, Philadelphia, PA, 19104, USA; VISN4 
      MIRECC, Crescenz Philadelphia VAMC, Philadelphia, PA, 19104, USA.
FAU - Levine, Eric S
AU  - Levine ES
AD  - Department of Neuroscience, University of Connecticut School of Medicine, 
      Farmington, CT, 06030, USA.
FAU - Covault, Jonathan
AU  - Covault J
AD  - Alcohol Research Center, Department of Psychiatry, University of Connecticut 
      School of Medicine, Farmington, CT, 06030-1410, USA; Institute for Systems 
      Genomics, University of Connecticut, Storrs, CT, 06268, USA. Electronic address: 
      jocovault@uchc.edu.
LA  - eng
GR  - K24 AA013736/AA/NIAAA NIH HHS/United States
GR  - M01 RR006192/RR/NCRR NIH HHS/United States
GR  - R01 AA015606/AA/NIAAA NIH HHS/United States
GR  - R01 AA023192/AA/NIAAA NIH HHS/United States
GR  - P60 AA003510/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170812
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0 (GABRA1 protein, human)
RN  - 0 (GABRD protein, human)
RN  - 0 (GABRG2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-A)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Adult
MH  - Alcoholism/genetics/*metabolism/pathology
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Ethanol/*toxicity
MH  - Female
MH  - Humans
MH  - Male
MH  - Membrane Potentials
MH  - Middle Aged
MH  - Neural Stem Cells/*drug effects/metabolism
MH  - Pluripotent Stem Cells/*drug effects/metabolism
MH  - RNA, Messenger/genetics/*metabolism
MH  - Receptors, GABA-A/*drug effects/genetics/metabolism
MH  - Up-Regulation
PMC - PMC5743620
MID - NIHMS921808
OTO - NOTNLM
OT  - Alcohol-use disorder
OT  - Electrophysiology
OT  - GABA receptor
OT  - Gene expression
OT  - Induced pluripotent stem cells
OT  - iPSC
COIS- conflicts of interest Dr. Kranzler has served as a consultant, CME speaker, or 
      advisory board member for the following companies: Indivior, Lundbeck, and 
      Pfizer. He is a member of the Alcohol Clinical Trials Group of the American 
      Society of Clinical Psychopharmacology, which is supported by Abbvie, Alkermes, 
      Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, Pfizer, and Xenoport.
EDAT- 2017/11/21 06:00
MHDA- 2018/09/18 06:00
PMCR- 2019/02/01
CRDT- 2017/11/21 06:00
PHST- 2017/03/21 00:00 [received]
PHST- 2017/08/03 00:00 [revised]
PHST- 2017/08/05 00:00 [accepted]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2018/09/18 06:00 [medline]
PHST- 2017/11/21 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - S0741-8329(17)30713-9 [pii]
AID - 10.1016/j.alcohol.2017.08.005 [doi]
PST - ppublish
SO  - Alcohol. 2018 Feb;66:45-53. doi: 10.1016/j.alcohol.2017.08.005. Epub 2017 Aug 12.