This proposal will address the relationship between ethanol insult and cell membrane ether lipids, primarily plasmalogens. The initial approach will be to correlate membrane ether lipid concentration and composition with ethanol exposure. The composition will be made in terms of total ethanol dose and period of exposure. The significance of ethanol induced membrane ether lipid modification will be assessed initially by correlation of concentration and composition with physical depenence and/or tolerance to ethanol. The possibility that alternatives in cell membrane ether lipid content may represent adaptation to ethanol insult will be evaluated by measuring the effect of plasmalogen concentration on physical properties (viscosity, phase transition and phase separation) of multilamellar liposomes, as well as well membrane fractions isolated from treated animals. The functional significance of membrane plasmalogens will also be evaluated by taking advantage of the observation that plasmalogen concentrations of fish central nervous system membranes can be manipulated by change in environment temperature. Thus, plasmalogen concentration can be altered independent of chronic ethanol exposure in an intact organism. The behavioral response to acute ethanol can then be measured independent of prior ethanol exposure and analyzed in regard to plasmalogen concentration and composition. The second phase of this investigation will address the mechanism or specific reaction in the metabolic pathway influenced by ethanol exposure. Relative contribution of synthesis or degradation to ethanol elicited changes in plasmalogen will be estimated using (1-14C) hexadecanol (1-14C) acetate and 14C-ethanolamine to label plasmalogen in the presence or absence of ethanol. The three different compounds would also allow prediction to be made concerning specific reaction(s) in the synthetic pathway which are inhibited or stimulated by ethanol. The initial experiments will be carried out using neuroblastoma cells maintained in culture. If specific lesions are identified in this system the reactions will be appraised using rat CNS tissue.
| Baker, R C (1987) Disassociation of cerebellar phospholipid composition and acute ethanol effects in mice selectively bred for differential sensitivity to ethanol. Alcohol Drug Res 7:291-9 |
| Ullman, M D; Baker, R C; Dietrich, R A (1987) Gangliosides of long sleep and short sleep mouse cerebellum and hippocampus and cerebellar and whole brain synaptosomal plasma membranes. Alcohol Clin Exp Res 11:158-62 |
| Rabin, R A; Baker, R C; Deitrich, R A (1987) Effects of chronic ethanol exposure on adenylate cyclase activities in the rat. Pharmacol Biochem Behav 26:693-7 |
| Palmer, M R; Basile, A S; Proctor, W R et al. (1985) Ethanol tolerance of cerebellar purkinje neurons from selectively outbred mouse lines: in vivo and in vitro electrophysiological investigations. Alcohol Clin Exp Res 9:291-6 |
