15 December 2000

Researchers from the Universities of Queensland and Texas have used a state-of-the-art analytic technique to determine for the first time how the pattern of gene expression in the human brain is affected by chronic alcoholism.

First results of the US$2.33 million (about AUD$4.32 million) study led by National Health and Medical Research Council (NHMRC) Principal Research Fellow Dr Peter Dodd of UQ's Biochemistry Department and Dr Adron Harris of the University of Texas Waggoner Centre will be published in the December issue of Alcoholism: Clinical & Experimental Research.

The study, also involving UQ Biochemistry Department Senior Research Fellow Dr Joanne Lewohl, sheds important new light on how long-term alcohol abuse affects the brain, and may lead to better treatments for alcoholism and other addictions.

The researchers used Gene Array technology (sometimes called "Gene Chips") to analyse thousands of RNA "messages" in the brains of 10 alcoholics and 10 non-alcoholics. More than 4000 gene products were analysed simultaneously. Of these, 163, or four percent, were found to differ by 40 percent or more between the alcoholics and non-alcoholics.

RNA, also called a "message", is made by genes and then used to make proteins. These proteins determine the appearance and function of each cell.

The new technology allowed researchers to determine which genes were being switched on or off (gene expression) in the brains of alcoholics. Previous technology allowed the analysis of only a handful of the more than 50,000 genes thought to be expressed in the brain.

Dr Dodd said the study showed that the genes most affected by alcoholism were related to the production of white matter (known as myelin) in the frontal cortex. This brain region is critical for judgement and decision-making.

"The results indicate that alcohol has a particular effect on myelin. Myelin forms an insulation sheath on information-carrying cells in the brain and its loss may contribute to the cognitive deficiencies associated with alcoholism," Dr Dodd said.

"These findings not only provide evidence for an extensive re-programming of brain gene expression due to alcoholism, but also identify several functional clusters of genes that are particularly affected by this disease.

"Just as a computer virus can change the programming of specific functions, our data show that chronic alcohol abuse can change the molecular programming and circuitry of the frontal cortex."

The study was funded for five years from August 2000 by the National Institutes of Health (NIH) USA with the UQ research team receiving US$934,234 (about AUD$1.73 million).

Key samples and diagnosis for the study were provided by the UQ team using the NHMRC Brain Bank's Brisbane node located in Dr Dodd's laboratory at UQ.

Dr Lewohl, who earlier completed postdoctoral research with Dr Harris at the Waggoner Centre, was a main protagonist in bringing the two research groups together two years ago.

For more information, contact Dr Peter Dodd (telephone 07 3365 3364), Dr Joanne Lewohl (telephone 07 3365 7320) or Shirley Glaister at UQ Communications (telephone 07 3365 2339).