Chronic alcohol consumption from adolescence-to-adulthood in mice--hypothalamic gene expression changes in the dilated cardiomyopathy signaling pathway.

Hong Zou,Guoping Zhao,Qinglian Xie,Meilei Jin,Yang Gao,Huaiguang Song,Lei Yu,Ke Wang,Huasheng Xiao

doi:10.1186/1471-2202-15-61

Abstract

BackgroundAdolescence is a developmental stage vulnerable to alcohol drinking-related problems and the onset of alcoholism. Hypothalamus is a key brain region for food and water intake regulation, and is one of the alcohol-sensitive brain regions. However, it is not known what would be the alcohol effect on hypothalamus following adolescent alcohol intake, chronically over the adolescent development, at moderate levels.ResultsWe employed a paradigm of chronic moderate alcohol intake from adolescence-to-adulthood in mice, and analyzed the alcohol effect on both behavioral and hypothalamic gene expression changes. A total of 751 genes were found and subjected to pathway analysis. The dilated cardiomyopathy (DCM) pathway was identified. The changes of ten genes under this pathway were further verified using RT-PCR. Chronic alcohol consumption during adolescence, even at moderate levels, led to a decrease of motor activity in mice, and also a concerted down regulation of signaling pathway initiating factor (SPIF) genes in the DCM signaling pathway, including β1-adrenergic receptor (Adrb1), Gs protein (Gnas), adenylyl cyclase 1 (Adcy1), and dihydropyridine receptor/L-type calcium channel (Cacna1d).ConclusionsThese findings suggest that adolescent alcohol intake may trigger gene expression changes in the CNS that parallel those found in the dilated cardiomyopathy signaling pathway. If such effects also take place in humans, our findings would serve as a warning against alcohol intake in youth, such as by teens and/or college students.

Highlights

Adolescence is a developmental stage vulnerable to alcohol drinking-related problems and the onset of alcoholism
Since the 10% alcohol solution contained higher amount of alcohol per unit volume than the 5% alcohol solution, we calculated the absolute amounts of alcohol consumption by mice from both the 5% alcohol group and the 10% alcohol group, and found that there was no significant difference for the absolute amount of alcohol consumed between the 5% vs. 10% alcohol groups
We studied ten genes in the dilated cardiomyopathy (DCM) pathway that were identified as differentially expressed genes (p < 0.05, showing 20% up- or down-regulation), as well as two other genes in the DCM pathway with “borderline” difference (Adrb1, p < 0.06, 0.78-fold change; Prkx, p < 0.03, 0.94-fold change) because of their key positions in the DCM pathway; in addition, Jup was tested, as an internal control, because it was among those identified by microarray analysis, but was not situated in the β1AR-dihydropyridine receptor (DHPR)-Ca2+ branch of the DCM pathway

Summary

Introduction

Adolescence is a developmental stage vulnerable to alcohol drinking-related problems and the onset of alcoholism. Hypothalamus is a key brain region for food and water intake regulation, and is one of the alcohol-sensitive brain regions. Adolescence is a critical transitional stage during which youth mature into adulthood. This developmental stage is characterized by a continued brain remodeling, a process that is sensitive to the disrupting effects of alcohol [1,2]. Being a key brain region for food and water intake regulation [16,17,18] and part of the reward system [19,20,21], the hypothalamus can modulate alcohol consumption and is involved in the development of alcoholism. Neuropeptides that are found in the hypothalamus could stimulate alcohol intake [24,25,26]

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