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Complex physical learning may compensate for prenatal alcohol exposure, study shows


Complex physical learning may help children overcome some mental disabilities that result from prenatal alcohol consumption by their mothers, say researchers whose experiments led to increased wiring in the brains of young rats.

In their study, infant rats were exposed to alcohol during a period of brain development (especially in the cerebellum) that is similar to that of the human third trimester of pregnancy. In adulthood, the rats improved their learning skills during a 20-day regimen of complex motor training, and generated new synapses in their cerebellum.

About 0.1 percent of U.S. births involve newborns with Fetal Alcohol Syndrome, characterized by a variety of physical, mental and neurological defects that often lead to behavioral, learning and mobility problems. Ten times that many children, also exposed to alcohol before birth, may not meet the diagnostic criteria for FAS but still have behavioral and brain defects that are now classified as alcohol-related developmental disorders.

Simply not drinking during pregnancy could prevent such damage, but a 1998 survey by the Centers for Disease Control and Prevention found both increasing rates of drinking by pregnant mothers and FAS in the last 15 years.

"The disorders associated with fetal exposure to alcohol are, by far, the leading known cause of mental retardation and developmental delay in this country and most others," said study co-author William T. Greenough, Swanlund Endowed Professor of Psychology at the University of Illinois at Urbana-Champaign. "In addition to the social cost, the economic cost is hundreds of billions of dollars each year. While it is, in principle, completely possible to prevent these disorders, this has not happened, even with increased public awareness. Hence it is critical to learn how to do as much as possible to improve the outcome for those affected by fetal alcohol exposure."

The study, published in the journal Brain Research, was led by Anna Y. Klintsova, a visiting professor of psychology and associate director of the fetal alcohol research laboratory at the Beckman Institute of Advanced Science and Technology at Illinois.

In the study, experimental groups of newborn rats that were suckling the normal diet of mother’s milk were given supplements with alcohol that achieved blood alcohol levels similar to binge drinking by pregnant women in the third trimester. Previous research has shown that many neurons (Purkinje cells) in the cerebellum are permanently destroyed by alcohol during this time.

After weaning, some of the alcohol-exposed rats and a control group of unexposed rats began the training, which involved learning to navigate increasingly difficult challenges involving motor skills. For 10 days, the alcohol-exposed rats made more errors than the control rats, but all of them improved and successfully completed the training exercise.

The researchers later examined the cerebellum of all the rats, finding the expected 30 percent loss of Purkinje cells in the alcohol-exposed rats. These neurons are the only ones that send signals to nerve cells outside of the cerebellar cortex. However, Klintsova said, the surviving neurons in the alcohol-exposed rats that went through the complex learning test had about 20 percent more synapses than all of the rats that did not train.

In a follow-up experiment, not reported in this study, the researchers tested the alcohol-exposed rats in a completely new motor-skills learning test. The rats that had undergone the previous training successfully learned the new skills at a level comparable to that done by control rats. More than half of the alcohol-exposed rats that did not receive the earlier training had to be removed from the experiment; none learned the new skills during the short period of testing.

"It may be that we did not challenge them enough to be able to detect significant differences still present from alcohol exposure," Klintsova said. "But we are very encouraged by what we saw, because we found, to our pleasure, that the alcohol-exposed animals that had undergone the complex motor learning behaved not significantly worse than the control animals."

Because the brain is more plastic, more changeable, early in life, Klintsova said, "the earlier you start intervention, the more benefits a child is likely to get."

"If a diagnosis is done early enough, and parents don’t hide the fact that the mother drank during the third trimester, then a physician can explain what may be happening," she said. "Then more effort could be put into the physical activity and complex learning environment for the children."

The researchers believe that an increase in the formation of synapses, the connections of communications, by neurons in the cerebellum led to the behavioral recovery of the alcohol-exposed rats. The cerebellum is responsible for coordinating very precise components involved in movement.

"A lot of damage can be done to the motor function, but it may be possible to rehabilitate these deficits if caught early enough," Klintsova said. "The children may not become champions, but they may be able to stand on the same playing field as their peers."

The National Institutes of Health funds the research. The NIH recently awarded a new five-year grant to continue the work. The funds will be divided among Klintsova, who has accepted a faculty appointment beginning in September at the State University of New York at Binghamton; Greenough at Illinois; and co-author Charles R. Goodlett at Indiana University-Purdue University in Indianapolis. The continuing research at Illinois will focus on the brain’s capacity to make new neurons during postnatal development and adulthood as a possible resource for therapeutic intervention, said Greenough, a professor of molecular and integrative physiology and of psychiatry in the College of Medicine.

Other researchers involved in the Brain Research study were former Illinois students Carly Scamra and Melissa Hoffman, and Ruth M.A. Napper of the University of Otago Medical School in Dunedin, New Zealand.

Jim Barlow | EurekAlert!
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