Tara L Teppen1,2, Harish R Krishnan1,2, Huaibo Zhang1,2, Amul J Sakharkar1,2, Subhash C Pandey1,3,2. 1. Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago IL 60612. 2. Jesse Brown Veterans Affairs Medical Center Chicago, IL 60612. 3. Anatomy and Cell Biology, University of Illinois at Chicago, Chicago IL 60612.
Abstract
BACKGROUND: The antianxiety effects of ethanol appear to be a crucial factor in promoting alcohol intake. Regulation of gene expression by microRNA (miRNA) is an important epigenetic mechanism that affects neuronal pathways and behaviors. We investigated the role of miRNAs underlying the mechanisms of ethanol-induced anxiolysis. METHODS: Acute ethanol-induced anxiolysis was measured in adult rats, and amygdaloid tissues were used for miRNA profiling by microarray analysis. The expression of miR-494 and its target genes in the amygdala was measured using real-time quantitative polymerase chain reaction. The direct role of miR-494 in the anxiety phenotype was also investigated via infusion of a miR-494 antagomir into the central nucleus of amygdala. RESULTS: Microarray profiling of miRNAs in the amygdala showed significant alteration of several miRNA expression levels by acute ethanol exposure. Expression of miR-494 was significantly decreased, whereas expression of the binding protein of cyclic adenosine monophosphate response element binding protein (CBP), p300, and Cbp/p300-interacting transactivator 2 (Cited2) was increased in the amygdala during ethanol-induced anxiolysis. Inhibition of miR-494 in the central nucleus of amygdala, through infusion of a specific antagomir, provoked anxiolysis, mimicking the action of ethanol. Also, expression of Cited2, CBP, and p300 as well as histone H3-lysine 9 acetylation was significantly increased by miR-494 antagomir infusion, indicating their regulation by miR-494 in the amygdala. CONCLUSIONS: These novel results suggest that acute ethanol-induced reduction in miR-494 expression in the amygdala can serve as a key regulatory mechanism for chromatin remodeling possibly leading to anxiolysis. Published by Elsevier Inc.
BACKGROUND: The antianxiety effects of ethanol appear to be a crucial factor in promoting alcohol intake. Regulation of gene expression by microRNA (miRNA) is an important epigenetic mechanism that affects neuronal pathways and behaviors. We investigated the role of miRNAs underlying the mechanisms of ethanol-induced anxiolysis. METHODS: Acute ethanol-induced anxiolysis was measured in adult rats, and amygdaloid tissues were used for miRNA profiling by microarray analysis. The expression of miR-494 and its target genes in the amygdala was measured using real-time quantitative polymerase chain reaction. The direct role of miR-494 in the anxiety phenotype was also investigated via infusion of a miR-494 antagomir into the central nucleus of amygdala. RESULTS: Microarray profiling of miRNAs in the amygdala showed significant alteration of several miRNA expression levels by acute ethanol exposure. Expression of miR-494 was significantly decreased, whereas expression of the binding protein of cyclic adenosine monophosphate response element binding protein (CBP), p300, and Cbp/p300-interacting transactivator 2 (Cited2) was increased in the amygdala during ethanol-induced anxiolysis. Inhibition of miR-494 in the central nucleus of amygdala, through infusion of a specific antagomir, provoked anxiolysis, mimicking the action of ethanol. Also, expression of Cited2, CBP, and p300 as well as histone H3-lysine 9 acetylation was significantly increased by miR-494 antagomir infusion, indicating their regulation by miR-494 in the amygdala. CONCLUSIONS: These novel results suggest that acute ethanol-induced reduction in miR-494 expression in the amygdala can serve as a key regulatory mechanism for chromatin remodeling possibly leading to anxiolysis. Published by Elsevier Inc.
Authors: Rosa M Crum; Lareina La Flair; Carla L Storr; Kerry M Green; Elizabeth A Stuart; Anika A H Alvanzo; Samuel Lazareck; James M Bolton; Jennifer Robinson; Jitender Sareen; Ramin Mojtabai Journal: Depress Anxiety Date: 2012-12-20 Impact factor: 6.505