Alcohol exposure during the developmental period induces α-endorphin neuronal death and causes alteration in the opioid control of stress axis function

Dipak K. Sarkar, Peter Kuhn, Jasson Marano, Cuiping Chen, Nadka Boyadjieva

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Proopiomelanocortin-producing neurons in the arcuate nucleus of the hypothalamus secrete β-endorphin (β-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 β-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 β-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-β1-linked apoptotic genes in β-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 β-EP neuronal perikarya in arcuate nuclei and in the number of β-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 β-EP to alter the lipopolysaccharide-induced CRH mRNA levels. These data suggest that ethanol exposure during the developmental period causes β-EP neuronal death by cellular mechanisms involving the suppression of cyclic AMP production and activation of TGF-β1-linked apoptotic signaling and produces long-term structural and functional deficiency of β-EP neurons in the hypothalamus.

Original languageEnglish (US)
Pages (from-to)2828-2834
Number of pages7
JournalEndocrinology
Volume148
Issue number6
DOIs
StatePublished - Jun 2007

All Science Journal Classification (ASJC) codes

  • Endocrinology

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