Chronic Binge-drinking Kills Neural Stem Cells

by Jim Schnabel

August 30, 2010

Adolescents who chronically binge-drink don’t just lose brain cells. They also lose the stem-like cells that replenish lost brain cells in a key memory-related region, according to a new study in young monkeys. The monkey results also suggest that an extended period of heavy drinking during adolescence can cause long term and possibly permanent impairment of the ability to learn and remember.

“Even 2 ½ months after they stopped drinking, we saw a 70 to 80 percent decrease in stem-like cells in these animals compared to the control animals,” says Chitra Mandyam, a neurobiologist at the Scripps Research Institute in La Jolla, Calif. Mandyam and Scripps neuropharmacologist Michael Taffe were the two senior investigators for the study, published on June 1 in the online edition of Proceedings of the National Academy of Sciences.

In most parts of the human brain, there are no neuronal stem or progenitor cells after the fetal stage of life; without this “neurogenesis” capability, mature neurons are not replaced when they die. But since 1998 researchers have known that in the hippocampus, a region crucial for spatial and verbal forms of memory, a population of neuronal stem cells does remain after birth and declines slowly throughout life.

Studies in the past decade have suggested that this precursor-cell population, which is proportionately larger in adolescents than adults, might be particularly vulnerable to chronic alcohol abuse. Studies of adolescent alcoholics found memory difficulties consistent with hippocampal damage; and a brain-imaging study published in 2000 revealed significant hippocampal shrinkage in adolescent and young adult alcoholics. Soon researchers began to report that alcohol could reduce hippocampal neurogenesis in rodents.

The new Scripps study aimed to confirm this as well as tease out the reason neurogenesis was impaired. To begin with, Mandyam, Taffe, and their colleagues gave four adolescent male rhesus macaque monkeys access to a strongly alcoholic fruit-flavored drink for an hour a day. During these sessions each monkey eagerly drank, on average, enough alcohol to become visibly intoxicated—in human terms seven to nine beers’ worth, says Mandyam. Three monkeys in a control group drank the same fruit-flavored beverage but without alcohol.

After eleven months of these daily binges, plus a drying-out period lasting between eight and ten weeks, the researchers compared the brains of the alcoholic and control groups.

The most striking finding in this comparison was that in the alcohol-exposed brains, the pool of neuronal stem-like cells in the hippocampus had largely disappeared. Even among mature hippocampal neurons, there were marked signs of degeneration, of a kind unlike that seen in the normal turnover of neurons, suggesting that alcohol was having a specific toxic effect.

“We don’t yet know why alcohol is toxic to these different groups of cells,” says Mandyam. “But something seems to be killing newly-born stem cells and increasing the degeneration of the existing neurons.”

“It’s a double-whammy, for lack of a better term,” says Kimberley Nixon, a researcher at the University of Kentucky who has been heavily involved in previous rodent model studies of impaired neurogenesis—studies that involved shorter alcohol exposures and thus showed more subtle effects. “Mandyam and Taffe’s group used a much longer exposure period, and the real strength of their work is that they used a primate, which is likely much more relevant to the human condition.”

Both groups now want to do further studies to determine more precisely how alcohol causes the depletion of neuronal stem cell populations, and whether these populations can fully recover after alcohol exposure ends. That work could lead to better treatments not only for alcoholism but also for other memory-related disorders and even depression, which has been linked to impairments in hippocampal neurogenesis.