Handhold Found for Alcohol's Grip on Brain
Findings May Lead to Agents that Prevent the Damage Alcohol Inflicts
It is estimated that one in 1,000 babies in the U.S. is born with fetal alcohol syndrome, characterized by mental and growth retardation, malformations of the brain and face, and behavioral disorders. Alcohol abuse can also lead to neurological disorders in adults, disrupting memory and learning. Michael Wilkemeyer, HMS instructor in neurology, and Michael Charness, HMS associate professor of neurology, director of the Alcohol Research Laboratory, and chief of neurology, both at the VA Boston Healthcare System, are leading research into how alcohol's effects on cell adhesion may be responsible for its effects on brain development.
Charness's group became interested in studying alcohol and cell adhesion after noting that children with mutations in the gene for the cell adhesion molecule L1 exhibit similar brain malformations as those with severe cases of fetal alcohol syndrome. Cell adhesion molecules are critical in guiding growth and migration of neurons and helping them form nerve bundles. Charness's group showed previously that ethanol in fairly low concentrations can inhibit cell adhesion mediated by L1.
In a paper published in the March 21 Proceedings of the National Academy of Sciences, the group finds that alcohols like ethanol, the alcohol in drinks, have a surprisingly specific interaction with L1. Like a tricky game of Twister, an alcohol molecule must bind to two different sites on L1 at once, a feat that can only be accomplished by certain alcohols like ethanol. Longer and bulkier alcohols like octanol are unable to align themselves correctly while more inflexible ones cannot bend as well to reach their targets. Not only are certain alcohols unable to interact with L1, they can actually block the effects of the active alcohols. The group found that low concentrations of octanol completely prevented ethanol's inhibition of cell adhesion. This discovery is a step toward developing drugs that can be used to prevent some of ethanol's damaging effects.