Premium
Period 2 Gene Deletion Abolishes β‐Endorphin Neuronal Response to Ethanol
Author(s) -
Agapito Maria,
Mian Nadia,
Boyadjieva Nadka I.,
Sarkar Dipak K.
Publication year - 2010
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.1530-0277.2010.01246.x
Subject(s) - per2 , proopiomelanocortin , medicine , beta endorphin , endocrinology , mutant , biology , in vivo , circadian rhythm , period (music) , circadian clock , hypothalamus , in vitro , wild type , gene , clock , biochemistry , genetics , physics , acoustics
Background: Ethanol exposure during early life has been shown to permanently alter the circadian expression of clock regulatory genes and the β‐endorphin precursor proopiomelanocortin (POMC) gene in the hypothalamus. Ethanol also alters the stress‐ and immune‐regulatory functions of β‐endorphin neurons in laboratory rodents. Our aim was to determine whether the circadian clock regulatory Per 2 gene modulates the action of ethanol on β‐endorphin neurons in mice. Methods: Per2 mutant ( mPer2 Brdml ) and wild type (C57BL/6J) mice were used to determine the effect of Per 2 mutation on ethanol‐regulated β‐endorphin neuronal activity during neonatal period using an in vitro mediobasal hypothalamic (MBH) cell culture model and an in vivo milk formula feeding animal model. The β‐endorphin neuronal activity following acute and chronic ethanol treatments was evaluated by measuring the peptide released from cultured cells or peptide levels in the MBH tissues, using enzyme‐linked immunosorbent assay (ELISA). Results: Per2 mutant mice showed a higher basal level of β‐endorphin release from cultured MBH cells and a moderate increase in the peptide content in the MBH in comparison with control mice. However, unlike wild type mice, Per 2 mutant mice showed no stimulatory or inhibitory β‐endorphin‐secretory responses to acute and chronic ethanol challenges in vitro. Furthermore, Per 2 mutant mice, but not wild type mice, failed to show the stimulatory and inhibitory responses of MBH β‐endorphin levels to acute and chronic ethanol challenges in vivo. Conclusions: These results suggest for the first time that the Per 2 gene may be critically involved in regulating β‐endorphin neuronal function. Furthermore, the data revealed an involvement of the Per 2 gene in regulating β‐endorphin neuronal responses to ethanol.