Alcoholism and alcohol abuse during pregnancy is the cause of important health problems both for the woman herself as well as for her passively dependent offspring, which may exhibit morphological, growth and neurobehavioral defects known as the Fetal Alcohol Syndrome. Mental retardation and delay in the development of the central nervous system are among the most common defects observed in offspring of alcohol abusing mothers. Recently, the endogenous opioid peptides have been shown to decrease the process of neurogenesis and brain growth. Thus it is the objective of this proposal to test the hypothesis that ethanol exerts some of its inhibitory effects on the neural growth by enhancing the activity of the brain and pituitary B-endorphin which is a powerful endogenous opioid peptide. To test this hypothesis two projects will be performed. In Project I the effect of ethanol on the ontogeny and activity of the B-endorphin system at various stages of fetal and post- natal life will be investigated by estimating the content of mRNA for proopiomelanocortin (the precursor for B-endorphin), the rate of biosynthesis of the B-endorphin related peptides, the content of B- endorphin peptides, and the relative proportions of the opiate active (non-acetyl) and opiate inactive (acetyl) forms of B-endorphin peptides in the pituitary gland and distinct regions of the brain. In Project II, the response of the brain and pituitary B-endorphin systems to cold and ether stress will be investigated. The proposed studies will provide information on how ethanol alters the activity of the brain and pituitary B-endorphin systems both under basal conditions and following exposure to stress. These ethanol induced changes on the activity of the brain and pituitary B-endorphin systems may mediate, at least in part, the ethanol induced decrease in neural growth. Since it is estimated that in the general population 1 to 3 of every 1000 live births have some problems associated with alcohol consumption during pregnancy, understanding the mechanisms involved in the ethanol induced neurobehavioral deficits is very important.
| Angelogianni, P; Li, H L; Gianoulakis, C (2000) Ontogenesis of proopiomelanocortin and its processing to beta-endorphin by the fetal and neonatal rat brain. Neuroendocrinology 72:231-41 |
