Opposing Actions of Ethanol and Nicotine on MicroRNAs are Mediated by Nicotinic Acetylcholine Receptors in Fetal Cerebral Cortical–Derived Neural Progenitor Cells

• DOI: 10.1111/j.1530-0277.2012.01793.x
• Publication Date: 2012-03-31T03:44:40Z
• Authors: Sridevi Balaraman; Ursula H. Winzer‐...; Rajesh C. Miranda
• Keywords: Mecamylamine; Methyllycaconitine

Background Ethanol ( EtOH ) and nicotine are often co‐abused. However, their combined effects on fetal neural development, particularly stem cells NSC s), which generate most neurons of the adult brain during second trimester pregnancy, poorly understood. We previously showed that influenced maturation in part, by suppressing expression specific micro RNA s (mi s). Here, we tested extent to coregulated known ‐sensitive R ‐9, mi ‐21, ‐153, ‐335), a nicotine‐sensitive ‐140‐3p), mRNA for nicotinic acetylcholine receptor nAChR subunits. Additionally, these were dependent. Methods Gestational day 12.5 mouse murine cerebral cortical–derived neurosphere cultures exposed , nicotine, mecamylamine, noncompetitive antagonist, individually or combination, short (24 hour) long (5 day) periods, mimic exposure vivo period neurogenesis. Levels s, ‐regulated transcripts, subunit assessed quantitative reverse transcription polymerase chain reaction. Results suppressed miR‐140‐3p, while at concentrations attained cigarette smokers induced dose‐related increase s. Nicotine's effect was blocked mecamylamine. Finally, decreased and, like prevented nicotine‐associated α4 β2 transcripts. Conclusions exert mutually antagonistic, ‐mediated teratogen‐sensitive These data suggest concurrent disrupts regulatory networks important maturation.