Public Release:  Studies suggest brain injury results from developmental exposure to alcohol, anesthesia, and lead

American Association for the Advancement of Science

SEATTLE, WA--Neuroapoptosis--the death of brain cells--may help explain a wide range of developmental disturbances, including fetal alcohol syndrome and schizophrenia, according to researchers who presented a symposium today at the 2004 AAAS (Triple-A-S) Annual Meeting. AAAS is the American Association for the Advancement of Science.

At the AAAS event, Columbia University psychiatrist Ezra Susser and his colleagues discussed new findings suggesting a link between exposure to lead in utero and a diagnosis of schizophrenia in young adults.

"The results of our study suggest that lead-induced prenatal damage to the developing brain may show itself decades following initial exposure to the substance," Susser said.

At the same symposium, Washington University psychiatrist, John W. Olney, released new research relating to the impact of pediatric medicines and alcohol on the developing brain. Previously, Olney and colleagues had reported that either alcohol or anesthetic drugs can cause large numbers of nerve cells to commit suicide in the developing rodent brain. Now they have determined that it requires only brief exposure to small amounts of these substances to trigger apoptosis. For example, exposure of the developing mouse brain to blood alcohol levels equivalent to those produced in a human from two cocktails was sufficient to cause the cells to die.

"Alcohol has been damaging the human fetal brain for centuries", Olney said, "but the link between alcohol and fetal brain damage was not recognized until 30 years ago. That alcohol damages the brain by driving neurons to commit suicide was discovered only very recently. Now, we are finding that anesthetic drugs can also have this effect, and Dr. Susser's findings raise the question whether the same is true for lead."

"Based on the evidence I have seen, it is quite certain that anesthetic drugs do delete nerve cells from the developing animal brain," said Olney, "But, to what extent the human brain is also sensitive to this mechanism remains to be determined. While this issue is being resolved, it is best to avoid exposing fetuses or infants to general anesthetics whenever possible. For example, elective surgical procedures should be postponed, and surgical procedures that are absolutely necessary can in some cases be performed under a local anesthetic, or possibly with the aid of pain-killing drugs that eliminate all pain but do not put a patient to sleep. Feasibility of the latter approach is currently under study." He added that there is currently no indication of risk to the fetus following short-term exposure to the epidurals that women use to relieve pain during labor.

Olney said that nerve cells are genetically programmed to commit suicide if they fail to make synaptic connection on time. Alcohol and anesthetic drugs interfere with the brain's neurotransmitter systems, thereby retarding the formation of synaptic connections. This automatically activates a signal within the nerve cell directing it to commit suicide, a form of cell death known as "apoptosis." Olney noted that the apoptosis mechanism operates only during synaptogenesis, a developmental period "when nerve cells are growing rapidly and forming synaptic contacts required for becoming integrated into complex neural networks." The human brain goes through synaptogenesis from the sixth-month of gestation through the first few years after birth, leaving a period of several years when immature neurons would be vulnerable.

Research by Olney and his colleagues suggests that alcohol and anesthetic drugs are particularly effective in triggering neuroapoptosis in the developing brain because they use a dual mechanism to suppress neuronal activity. These substances decrease the amount of glutamate excitatory transmitter input, while increasing the amount of GABA inhibitory transmitter input - both actions tend to put nerve cells out of commission, so that they cannot tend to their task of forming synaptic connections. Other drugs that trigger neuroapoptosis in the developing brain are used as sedatives and anticonvulsants; some are drugs that women abuse while pregnant.

Olney and Susser noted that more work is needed to demonstrate whether lead has the same effect on the developing brain as the substances tested by Olney and his research group. "We're identifying factors that are most likely to cause apoptosis, and we're looking to see how it relates to schizophrenia," said Susser, whose work recently was published online in the journal Environmental Health Perspectives (M. Opler, A. Brown, J. Graziano, et al, "Prenatal Lead Exposure, d- Aminolevulinic Acid, and Schizophrenia." In Press).

Olney and Susser indicated that they view developmental neuroapoptosis as a "final common pathway" type of mechanism which, regardless how it is activated, has considerable potential to disrupt brain development and give rise to a wide variety of neuropsychiatric disturbances.

In applying his findings to humans, Olney points to the work of Ann P. Streissguth, who also is one of the speakers on the panel. Streissguth has followed the impact of maternal alcohol use on the offspring of a group of women who were pregnant in 1974. She will report findings on the extent of "secondary disabilities" in people with fetal alcohol syndrome and fetal alcohol effects, noting that 90 percent of people exposed to alcohol in the womb reported mental health problems.

"Many had attention deficit problems, strikingly high psychoses, suicide attempts and suicide ideation," Streissguth said.

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The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journal, Science (www.sciencemag.org). AAAS was founded in 1848, and serves some 265 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of one million. The non-profit AAAS (www.aaas.org) is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy; international programs; science education; and more. For the latest research news, log onto EurekAlert!, www.eurekalert.org, the premier science-news Web site, a service of AAAS.

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MEDIA NOTE: A news briefing on this research will take place at 3:00 p.m. Pacific Time, Friday, 13 February, during the AAAS Annual Meeting in Seattle, in the Eliza Anderson Amphitheater, Grand Hyatt Hotel. Further, these and other speakers will take part in a symposium titled, "Pediatric Medicines and Alcohol Cause Developing Neurons to Commit Suicide," at 9:00 a.m. Saturday, 14 February, in the second floor of the Sheraton Hotel, West Ballroom A.

Press registration is located in the AAAS Press Center in Leonesa I of the Grand Hyatt Hotel.

AAAS is the world's largest general scientific society, dedicated to "Advancing science, Serving society."

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