Sobering Work - fetal alcohol syndrome research

Science News, July 8, 2000 by Damaris Christensen

Unraveling alcohol's effects on the developing brain

At parties, young women often want to talk to James R. West. Sure, he's a charming guy, but they especially want to talk about his work--and how it may touch them personally. The issue is potentially close at hand: West studies the effects of alcohol on a baby's developing brain.

"People always ask me, How much is too much?" says West, a neurobiologist at the Texas A&M University Health Science Center in College Station. "We don't really know."

A decade ago, scientists thought there would be a straightforward answer. But recent findings indicate that alcohol doesn't have a single threshold as it acts on different biochemical pathways and different parts of the brain. So, it isn't clear when and where in human fetuses the trouble starts.

Fetal alcohol syndrome was first described in France in the late 1960s and in the United States a few years later. The condition was difficult to recognize because not every woman who drinks heavily during pregnancy bears a baby with the characteristic physical and behavioral abnormalities.

Today, out of each 10,000 children born in the United States, between 3 and 30 suffer from fetal alcohol syndrome. These babies are small at birth, with distinctive facial features, including a flattened area between the nose and upper lip, narrow upper lips, small eyes and noses, and narrow foreheads.

Their mother's drinking has affected their central nervous system as well: Fetal alcohol syndrome is the leading cause of nonhereditary mental retardation.

Children with the outward signs of the syndrome may represent only the most severe example of a spectrum of detrimental effects. Alcohol-exposed children who lack the characteristic facial features of fetal alcohol syndrome may still suffer from attention problems, hyperactivity, aggression, and psychiatric illnesses. Some youngsters may have trouble functioning independently, though they have normal intelligence as measured by IQ tests.

Many recent studies indicate that alcohol doesn't uniformly interfere with the function of every cell in a fetal brain. Sensitive imaging techniques have revealed that alcohol damages some parts of the developing human brain more than others.

Moreover, it targets particular biochemical pathways vital to the development, function, migration, and survival of certain nerve cells, says Kenneth Warren of the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Md. No single mechanism is likely to account for all of the structural, functional, and behavioral problems that have been attributed to prenatal alcohol exposure, he says.

The ultimate goal of research in this area is to identify new ways of blocking or mediating some of alcohol's harmful effects, says Warren. Better knowledge of underlying mechanisms may help researchers figure out how to rescue cells or predict which infants are most at risk from alcohol exposure, he says.

When researchers started looking at the brains of youngsters with fetal alcohol syndrome, the damage seemed so pervasive that the investigators assumed alcohol must affect every system in the developing brain. For example, alcohol might disrupt cell function by altering the integrity of the membranes. Alternatively, alcohol might damage or kill cells indiscriminately by increasing the production of free radicals, toxic byproducts of oxygen metabolism.

"One of the major changes in the alcohol field in the last 10 years has been the identification of proteins that alcohol might interact with directly," says Michael E. Charness of Harvard Medical School in Boston. For example, researchers have identified specific effects on molecules that regulate development and others that participate in cell signaling.

The cell-adhesion molecule called L1 guides cell migration in the developing brain. This protein regulates nerve-cell adhesion and movement, processes critical to getting the cells to their proper position in a developing brain. Charness and his colleagues gave specific nerve cells growing in laboratory cultures alcohol concentrations equivalent to those resulting when a woman has one to two drinks. This alcohol can prevent nerve cells guided by L1 from adhering to each other, Charness says.

In a pregnant woman, this effect may interfere with the fetus's developmental steps, he says. Whether these changes would be significant enough to disrupt brain function in people or animals, however, is still unknown.

Ethanol is the alcohol in beer, wine, and other drinks. In experiments reported in the March 28 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, Charness and his colleagues found that some other forms of alcohol, such as octanol, can block ethanol's action. Their results suggest that ethanol targets a specific area on L1, Charness says.

Besides encouraging cell adhesion, L1 can trigger nerve cells to grow toward each other and form connections. Ethanol concentrations mimicking a woman's exposure to a single glass of wine seem to slow the growth of such connections, reports Cynthia F. Bearer of Case Western Reserve University School of Medicine in Cleveland.