This Article Full Text Full Text (PDF) All Versions of this Article: 148/6/2828    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sarkar, D. K. Articles by Boyadjieva, N. Search for Related Content PubMed PubMed Citation Articles by Sarkar, D. K. Articles by Boyadjieva, N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB ETHANOL Medline Plus Health Information Stress

Alcohol Exposure during the Developmental Period Induces ß-Endorphin Neuronal Death and Causes Alteration in the Opioid Control of Stress Axis Function

Endocrinology Program, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901

Address all correspondence and requests for reprints to: Dipak K. Sarkar, Endocrinology Program, Rutgers, The State University of New Jersey, 84 Lipman Drive, New Brunswick, New Jersey 08901. E-mail: sarkar{at}aesop.rutgers.edu.

Proopiomelanocortin-producing neurons in the arcuate nucleus of the hypothalamus secrete ß-endorphin (ß-EP), which controls varieties of body functions including the feedback regulation of the CRH neuronal activity in the paraventricular nucleus of the hypothalamus. Whether ethanol exposure in developing rats induces ß-EP neuronal death and alters their influence on CRH neurons in vivo has not been determined. We report here that binge-like ethanol exposures in newborn rats increased the number of apoptotic ß-EP neurons in the arcuate nucleus of the hypothalamus. We also found that immediately after ethanol treatments there was a significant reduction in the expression of proopiomelanocortin and adenylyl cyclases mRNA and an increased expression of several TGF-ß1-linked apoptotic genes in ß-EP neurons isolated by laser-captured microdissection from arcuate nuclei of young rats. Several weeks after the ethanol treatment, we detected a reduction in the number of ß-EP neuronal perikarya in arcuate nuclei and in the number of ß-EP neuronal terminals in paraventricular nuclei of the hypothalamus in the treated rats. Additionally, these rats showed increased response of the hypothalamic CRH mRNA to the lipopolysaccharide challenge. The ethanol-treated animals also showed incompetent ability to respond to exogenous ß-EP to alter the lipopolysaccharide-induced CRH mRNA levels. These data suggest that ethanol exposure during the developmental period causes ß-EP neuronal death by cellular mechanisms involving the suppression of cyclic AMP production and activation of TGF-ß1-linked apoptotic signaling and produces long-term structural and functional deficiency of ß-EP neurons in the hypothalamus.