The recent availability of reliable feasible techniques for isolating, growing and maintaining primary glial cells, of high purity, in culture has dramatically expanded knowledge on the neurobiological substrates and behavior of these cells. The primary objective of this proposal, on which there is currently virtually no information, is to study the effects of acute and chronic exposure of ethanol and of its withdrawal on astrocytes derived from neonatal rat brain. The main aim is to delineate how activation of the phosphoinositide (PI) pathway through the adrenergic system is altered in ethanol exposed cells. Specifically, stimulation of adrenergic receptor subtypes on PI hydrolysis will be determined as well as the effects of cyclic (c)- AMP augmenting agents, K+, and Ca2+-channel agonists and antagonists on this signal-generating system. In addition, ethanol- induced alterations in the characteristics of specific adrenergic receptors will be ascertained and the effects of norepinephrine- induced c-AMP accumulation and the enzymes involved in c-AMP metabolism (adenylate cyclase and phosphodiesterase) will be determined. Finally, changes in Ca2+ fluxes induced by adrenergic substances and alterations in the binding characteristics of Ca2+-channel antagonists will be compared in ethanol-explosed and control astrocytes. Glial cells constitute a large bulk of CNS cells and their interactions with neurons, both passively and actively, determine the integrated response of these various neural cell types and ultimately the biobehavioral output of the brain. As an initial step in understanding the short-term and long-term effects of alcohol on the brain, the present proposal hopes to provide knowledge as to how key signaling systems and processes involved in the functioning of astrocytes are altered by this drug. The long-term objective is to gain a fundamental understanding of how ethanol-induced alterations in the CNS produce their maladaptive and frequently destructive behaviors.
| Rosenberg, A; Noble, E P (1993) Inhibition of neuritogenic ganglioside biosynthesis in chick brain neurons by calcium ionophore A23187. Biochem Biophys Res Commun 190:522-8 |
| Ritchie, T; Rosenberg, A; Noble, E P (1992) Regulation of phosphoinositide hydrolysis in cultured astrocytes by sphingosine and psychosine. Biochem Biophys Res Commun 186:790-5 |
| Rosenberg, A; Sauer, A; Noble, E P et al. (1992) Developmental patterns of ganglioside sialosylation coincident with neuritogenesis in cultured embryonic chick brain neurons. J Biol Chem 267:10607-12 |
| Rosenberg, A; Noble, E P (1989) EGF-induced neuritogenesis and correlated synthesis of plasma membrane gangliosides in cultured embryonic chick CNS neurons. J Neurosci Res 24:531-6 |
| Noble, E P; Ritchie, T (1989) Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus. Life Sci 45:803-10 |
