People who make the transition from moderate drinkers to problem drinkers may have their genes to blame, according to new research. Researchers at the University of California, San Francisco (UCSF) have found that a tiny segment of genetic material known as a microRNA plays a central role in the transition from moderate drinking to binge drinking and other alcohol use disorders.
Previous research in the UCSF laboratory of Dorit Ron, Endowed Chair of Cell Biology of Addiction in Neurology, has demonstrated that the level of a protein known as brain-derived neurotrophic factor, or BDNF, is increased in the brain when alcohol is consumed in moderation.
In turn, experiments in Ron's lab have shown, BDNF prevents the development of alcohol use disorders. In the new study, Ron and first author Emmanuel Darcq, a
former post-doctoral fellow now at McGill University in Canada, found that when mice consumed excessive amounts of alcohol for a prolonged period, there was a marked decrease in the amount of BDNF in the medial prefrontal cortex (mPFC), a brain region important for decision making.
The decline was associated with a corresponding increase in the level of a microRNA called miR-30a-5p. MicroRNAs lower the levels of proteins such as BDNF by binding to messenger RNA, the molecular middleman that carries instructions from genes to the protein-making machinery of the cell, and tagging it for destruction.
Ron and colleagues then showed that if they increased the levels of miR-30a-5p in the mPFC, BDNF was reduced, and the mice consumed large amounts of alcohol. When mice were treated with an inhibitor of miR-30a-5p, however, the level of BDNF in the mPFC was restored to normal and alcohol consumption was restored to normal, moderate levels.
"Our results suggest BDNF protects against the transition from moderate to uncontrolled drinking and alcohol use disorders," said Ron, senior author of the study and a professor in UCSF's Department of Neurology. "When there is a breakdown in this protective pathway, however, uncontrolled excessive drinking develops, and microRNAs are a possible mechanism in this breakdown.
"This mechanism may be one possible explanation as to why 10% of the population develop alcohol use disorders and this study may be helpful for the development of future medications to treat this devastating disease," said Ron. The study was published in the journal Molecular Psychiatry.