The basic rationale for this proposed research is derived from the recent discoveries that alcohol dissolves into cell membranes, where it fluidizes and presumably disorients many of the molecules that are imbedded in the lipid bilayer. It seems reasonable to suspect that disorientation of embedded molecules would alter their normal functions. Because these functions can involve synaptic transmission, I postulate that some of the physiological and behavioral consequences of alcohol are indirect consequences of this initial molecular disorientation. One class of functionally important molecules that are embedded in the bilayer, and thus likely to be disordered, is a family of compounds known as gangliosides. The terminal end groups of gangliosides, known as sialic acids (SA), have previously been shown to be altered by alcohol, and it is thus likely that alcohol is acting on the ganglioside source of this SA. In fact, preliminary data are present herein to support this hypothesis. The proposed research will evaluate the replicability of these initial observations, and extend them to evaluate dose response, sex differences, age differences, comparisons of a single dose vs. """"""""binge"""""""" drinking, and the relationship to development of tolerance in both adults and in simulated fetal alcohol syndrome. Mechanisms whereby these effects are produced will be investigated in several ways, including determination of how acute and chronic alcohol effects might be modified by pre-treatment with gangliosides or SA precursor. Also, synthesis and degradation dynamics will be examined to help explain how the alcohol effects are occurring.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006920-03
Application #
3110357
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1986-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1990-03-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Gilmore, N; Cherian, L; Klemm, W R (1991) Ganglioside or sialic acid attenuates ethanol-induced decrements in locomotion, nose-poke exploration, and anxiety, but not body temperature. Prog Neuropsychopharmacol Biol Psychiatry 15:91-104
Klemm, W R (1990) Dehydration: a new alcohol theory. Alcohol 7:49-59
Cherian, L; Klemm, W R (1990) Effect of acute injections of ethanol on lipid and protein-bound sialic acid in mice of different ages. Drug Alcohol Depend 26:29-34
Mathew, J; Klemm, W R (1989) Differences in susceptibility of rat liver and brain sialidases to ethanol and gangliosides. Pharmacol Biochem Behav 33:797-803
Foster, D M; Huber, M D; Klemm, W R (1989) Ethanol may stimulate or inhibit (Na+ + K+)-ATPase, depending upon Na+ and K+ concentrations. Alcohol 6:437-43
Cherian, L; Mathew, J; Klemm, W R (1989) Ethanol-induced hydrolysis of brain sialoglycoconjugates in the rat: effect of sialic acid in antagonizing ethanol intoxication. Alcohol Clin Exp Res 13:435-8
Mathew, J; Klemm, W R (1988) Ethanol promotes hydrolysis of 3H-labeled sialoconjugates from brain of mice in vitro. Alcohol 5:499-503
Klemm, W R; Boyles, R; Mathew, J et al. (1988) Gangliosides, or sialic acid, antagonize ethanol intoxication. Life Sci 43:1837-43
Klemm, W R; Mathew, J; Maring, R G (1988) Acute alcohol decreases gangliosides in mouse brain. Alcohol 5:215-9
Klemm, W R (1987) Membrane glycoconjugates as potential mediators of alcohol effects. Prog Neuropsychopharmacol Biol Psychiatry 11:633-58