Background: 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. 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.
Results: We 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 beta 1-adrenergic receptor (Adrb1), Gs protein (Gnas), adenylyl cyclase 1 (Adcy1), and dihydropyridine receptor/L-type calcium channel (Cacna1d).
Conclusions: These 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.
[1]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
[2]Fudan Univ, Sch Life Sci, Dept Microbiol, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[3]Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China.
[4]Natl Engn Res Ctr Biochip Shanghai, Chinese Natl Human Genome Ctr Shanghai, Shanghai MOST Key Lab Dis & Hlth Genom, Shanghai, Peoples R China.
[5]Shanghai Tradit Med Univ, Shu Guang Hosp, Shanghai, Peoples R China.
[6]Chinese Univ Hong Kong, Prince Wales Hosp, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China.
[7]Chinese Univ Hong Kong, Prince Wales Hosp, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.
[8]Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA.
[9]Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08854 USA.
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