University of Iowa researchers who seek to reduce fetal alcohol syndrome cases -- which annually number nearly 8,800 in the United States -- have received a major grant to study how a certain pathway in the brain protects against the toxic effects of alcohol. The two-year, $387,187 grant is funded by the National Institute of Alcohol Abuse and Alcoholism, part of the National Institutes of Health.
Fetal alcohol exposure damages the nervous system and can cause irreversible brain dysfunction, including mental retardation, epilepsy, and attention deficit hyperactivity disorder, said the project's principal investigator, Bahri Karaçay, Ph.D., associate research scientist in pediatrics in the UI Roy J. and Lucille A. Carver College of Medicine.
"Inherent signaling mechanisms in the central nervous system can prevent the damaging effects of such insults as alcohol. However, alcohol consumption during pregnancy can overwhelm these protective measures and damage the fetus, as we see in fetal alcohol syndrome," Karaçay said. "Our research goal is to find genes and pathways that constitute this neuroprotective system, so we can use that information to prevent the toxic effects."
The study co-investigator is Daniel Bonthius, M.D., Ph.D., UI professor of pediatrics, a physician with Children's Hospital of Iowa and recently elected president of the National Fetal Alcohol Syndrome Group, a satellite organization of the Research Society on Alcoholism.
The UI study builds on a research collaboration by Bonthius, Karaçay and Nicholas Pantazis, Ph.D., UI professor of anatomy and cell biology, and utilizes mouse and rat models. The team's investigations have shown that neurons from the cerebellum, the brain region that helps integrate sensory perception and muscle movement, are sensitive to alcohol during early development, but later become resistant.
"This change indicates that there must be some protective mechanism in the brain that matures over time," Karaçay said. "Other studies have suggested that vasoactive intestinal peptide and its downstream signaling pathway, called the cAMP pathway, are neuroprotective, so we are examining whether they together regulate genes that may protect against fetal alcohol syndrome."
Vasoactive intestinal peptide was first discovered in swine intestines, hence its name. However, scientists later learned that it functions in a variety of organs, including the brain. The peptide activates the cAMP pathway, or cyclic adenosine monophosphate pathway, which plays an important role in how cells signal one another.
The team will utilize neonatal rodents for the current study. The first one to two weeks of rodent life are equivalent to the third trimester of human gestation.
"The third trimester of a human pregnancy is when the fetal brain growth spurt takes place, thus alcohol is particularly damaging in the brain at that time," Karaçay said. "However, the brain is vulnerable to alcohol-induced damage throughout development. Based on all the scientific data, the U.S. Surgeon General has said that there is no known safe time for alcohol consumption during pregnancy."
While overall rates of alcohol use among pregnant women have declined since 1995, rates of frequent and binge drinking remain at high levels. Nearly one in 30 pregnant women reports "risk drinking" -- seven or more drinks per week or five or more drinks at one occasion -- according to a fact sheet by the National Center on Birth Defects and Developmental Disabilities, part of the Centers for Disease Control (CDC).
In addition, the CDC reports that half of all pregnant women say they use alcohol, yet half of all pregnancies are unplanned -- troubling statistics, as birth defects associated with alcohol exposure can occur at any point during a pregnancy, even before a woman knows she pregnant.
"Fetal alcohol syndrome is a major public health problem. A human fetus is far more vulnerable than an adult to brain injury due to alcohol exposure," Karaçay said. "In our studies, we aim to learn more about fetal alcohol resistance and vulnerability, and we hope that this knowledge can ultimately be used to prevent fetal alcohol syndrome."
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STORY SOURCE: University of Iowa Health Science Relations, 5137 Westlawn, Iowa City, Iowa 52242-1178
PRONUNCIATION NOTE: Bahri Karaçay is pronounced "BAH-ree CAR-uh-chi" (the "i" sounds like the "ie" in "pie").