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Evidence for Possible P eriod 2 Gene Mediation of the Effects of Alcohol Exposure During the Postnatal Period on Genes Associated with Maintaining Metabolic Signaling in the Mouse Hypothalamus
Author(s) -
Agapito Maria A.,
Barreira Jacklin C.,
Logan Ryan W.,
Sarkar Dipak K.
Publication year - 2013
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2012.01871.x
Subject(s) - proopiomelanocortin , hypothalamus , endocrinology , medicine , period (music) , circadian rhythm , biology , melanin concentrating hormone , prohormone , gene , hormone , circadian clock , mutant , neuropeptide , genetics , receptor , physics , acoustics
Background Animals exposed to alcohol during the developmental period develop circadian disturbances and metabolic problems that often persist during their adult period. In order to study whether alcohol and the circadian clock interact to alter metabolic signaling in the hypothalamus, we determined whether postnatal alcohol feeding in mice permanently alters metabolic sensing in the hypothalamus. Furthermore, we evaluated whether the effect of circadian disruption via P eriod 2 ( Per 2 ) gene mutation prevents alcohol's effects on metabolic signaling in the hypothalamus. Methods Per 2 mutant and wild‐type male and female mice of the same genetic background were given a milk formula containing ethanol ( E t OH ; 11.34% vol/vol) from postnatal day (PD) 2 to 7 and used for gene expression and peptide level determinations in the hypothalamus at PD 7 and PD 90. Results We report here that postnatal alcohol feeding reduces the expression of proopiomelanocortin ( Pomc ) gene and production of β‐endorphin and α‐melanocyte stimulating hormone (α‐ MSH ) in the hypothalamus that persists into adulthood. In addition, expressions of metabolic sensing genes in the hypothalamus were also reduced as a consequence of postnatal alcohol exposure. These effects were not sex‐specific and were observed in both males and females. Mice carrying a mutation of the Per 2 gene did not show any reductions in hypothalamic levels of Pomc and metabolic genes and β‐endorphin and α‐ MSH peptides following alcohol exposure. Conclusions These data suggest that early‐life exposure to alcohol alters metabolic sensing to the hypothalamus possibly via regulating Per 2 gene and/or the cellular circadian clock mechanism.