Researchers at the University at Buffalo studying the effects of alcohol on the brain, using zebrafish as a model, have identified several novel central nervous system proteins that are affected by chronic alcohol exposure.
They also confirmed the involvement of additional proteins previously suggested as targets of alcohol toxicity, and observed abnormal behavior in the fish resulting from chronic alcohol exposure.
Results of the research appeared in the Aug. 15 online edition of the European Journal of Pharmacology.
Five proteins were found to be overexpressed and three were found to be underexpressed. These proteins are thought to be involved in critical mechanisms such as programmed cell death, cholesterol balance, amino acid metabolism, oxidative stress and signal transduction.
"Identification of proteins that show selective changes in abundance after alcohol exposure has the potential to unlock new pathways both for understanding the mechanisms of alcoholism and alcohol toxicity, as well as its amelioration," said Richard A. Rabin, Ph.D., professor in the UB Department of Pharmacology and Toxicology and senior author on the study.
Senthilkumar Damodaran, doctoral student in pharmacology, is first author.
The study involved 16 long-fin striped zebrafish, in two trials of eight each, which were placed as a group in a tank with ethyl alcohol for four weeks. Rabin said the researchers chose zebrafish because they are easy to breed and maintain, their DNA sequences are similar to that of humans and they are sensitive to alcohol concentrations.
The concentration of alcohol used is similar to alcohol levels observed in humans, Rabin noted, and is comparable to levels reported in several rodent studies.
"Exposing the fish to alcohol for four weeks has the virtue of being a simple system," he said. "The ethanol concentration and length of exposure can be controlled tightly and applied identically to all subjects. This method also prevents possible complications due to alcohol withdrawal." He noted, however, that it does not reflect the typical situation in humans.