PMID- 24416161 OWN - NLM STAT- MEDLINE DCOM- 20140908 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 1 DP - 2014 TI - Long-term effects of peripubertal binge EtOH exposure on hippocampal microRNA expression in the rat. PG - e83166 LID - 10.1371/journal.pone.0083166 [doi] LID - e83166 AB - Adolescent binge alcohol abuse induces long-term changes in gene expression, which impacts the physiological stress response and memory formation, two functions mediated in part by the ventral (VH) and dorsal (DH) hippocampus. microRNAs (miRs) are small RNAs that play an important role in gene regulation and are potential mediators of long-term changes in gene expression. Two genes important for regulating hippocampal functions include brain-derived neurotrophic factor (BDNF) and sirtuin-1 (SIRT1), which we identified as putative gene targets of miR-10a-5p, miR-26a, miR-103, miR-495. The purpose of this study was to quantify miR-10a-5p, miR-26a, miR-103, miR-495 expression levels in the dorsal and ventral hippocampus of male Wistar rats during normal pubertal development and then assess the effects of repeated binge-EtOH exposure. In addition, we measured the effects of binge EtOH-exposure on hippocampal Drosha and Dicer mRNA levels, as well as the putative miR target genes, BDNF and SIRT1. Overall, mid/peri-pubertal binge EtOH exposure altered the normal expression patterns of all miRs tested in an age- and brain region-dependent manner and this effect persisted for up to 30 days post-EtOH exposure. Moreover, our data revealed that mid/peri-pubertal binge EtOH exposure significantly affected miR biosynthetic processing enzymes, Drosha and Dicer. Finally, EtOH-induced significant changes in the expression of a subset of miRs, which correlated with changes in the expression of their predicted target genes. Taken together, these data demonstrate that EtOH exposure during pubertal development has long-term effects on miRNA expression in the rat hippocampus. FAU - Prins, Sarah A AU - Prins SA AD - Loyola University Chicago Health Science Division, Department of Cell and Molecular Physiology, Maywood, Illinois, United States of America. FAU - Przybycien-Szymanska, Magdalena M AU - Przybycien-Szymanska MM AD - Loyola University Chicago Health Science Division, Department of Cell and Molecular Physiology, Maywood, Illinois, United States of America. FAU - Rao, Yathindar S AU - Rao YS AD - Loyola University Chicago Health Science Division, Department of Cell and Molecular Physiology, Maywood, Illinois, United States of America. FAU - Pak, Toni R AU - Pak TR AD - Loyola University Chicago Health Science Division, Department of Cell and Molecular Physiology, Maywood, Illinois, United States of America. LA - eng GR - T32 AA013527/AA/NIAAA NIH HHS/United States GR - R01 AA021517/AA/NIAAA NIH HHS/United States GR - R21AA018398/AA/NIAAA NIH HHS/United States GR - R01AA021517/AA/NIAAA NIH HHS/United States GR - R21 AA018398/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140108 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 3K9958V90M (Ethanol) RN - 3XMK78S47O (Testosterone) SB - IM MH - Aging/drug effects/genetics MH - Animals MH - Binding Sites/genetics MH - Binge Drinking/*genetics MH - Ethanol/*adverse effects MH - *Gene Expression Regulation/drug effects MH - Hippocampus/drug effects/growth & development/*metabolism MH - Male MH - MicroRNAs/biosynthesis/*genetics MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Sexual Maturation/drug effects/*genetics MH - Testosterone/blood MH - Time Factors PMC - PMC3885403 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/01/15 06:00 MHDA- 2014/09/10 06:00 PMCR- 2014/01/08 CRDT- 2014/01/14 06:00 PHST- 2013/09/20 00:00 [received] PHST- 2013/10/30 00:00 [accepted] PHST- 2014/01/14 06:00 [entrez] PHST- 2014/01/15 06:00 [pubmed] PHST- 2014/09/10 06:00 [medline] PHST- 2014/01/08 00:00 [pmc-release] AID - PONE-D-13-38888 [pii] AID - 10.1371/journal.pone.0083166 [doi] PST - epublish SO - PLoS One. 2014 Jan 8;9(1):e83166. doi: 10.1371/journal.pone.0083166. eCollection 2014.