Low ethanol concentration alters CHRNA5 RNA levels during early human development.
Alcohol use is common and consumption during pregnancy has been shown to lead to a myriad of physical and neurologic abnormalities commonly referred to as fetal alcohol spectrum disorder. Substance addiction, which includes alcohol, has been shown to involve the major nicotinic acetylcholine receptor subunit CHRNA5. Using human embryonic stem cells as a model of early human development, we show that low concentrations of ethanol (20mM) can alter the expression of CHRNA5. Changes in CHRNA5 expression is linked to altered GABA and NMDA receptor expression, as well as abnormal development of the frontal cortex. These results suggest that alcohol exposure can alter early neurologic development, which may favor addiction and other developmental abnormalities in unborn children.
Krishnamoorthy
Malini
M
Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Gerwe
Brian A
BA
Scharer
Christopher D
CD
Heimburg-Molinaro
Jamie
J
Gregory
Frederick
F
Nash
Rachel J
RJ
Arumugham
Jagan
J
Stewart
Bethany
B
Stice
Steven L
SL
Nash
Rodney J
RJ
D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D055106:Genome-Wide Association Study; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D013997:Time Factors
C447158:CHRNA5 protein, human; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D000431:Ethanol; D012313:RNA