BETHESDA, Md. (August 11, 2008) − In a study on fetal alcohol syndrome, researchers were able to prevent the damage that alcohol causes to cells in a key area of the fetal brain by blocking acid sensitive potassium channels and preventing the acidic environment that alcohol produces. The cerebellum, the portion of the brain that is responsible for balance and muscle coordination, is particularly vulnerable to injury from alcohol during development.
The researchers also found that although alcohol lowers the amount of oxygen in the blood of the mother, it is not the lack of oxygen that damages the fetal cerebellum, but the drop in pH.
The study with sheep, published in the August issue of the American Journal of Physiology, demonstrated that the damage can be prevented by blocking acid sensitive potassium channels, known as TASK channels, that lead into the Purkinje cells. The study, "Acid Sensitive Channel Inhibition Prevents Fetal Alcohol Spectrum Disorders Cerebellar Purkinje Cell Loss," was carried out by Jayanth Ramadoss, Emilie R. Lunde, Nengtai Ouyang, Wei-Jung A. Chen and Timothy A. Cudd. The research was done at Texas A&M University.
Fetal Alcohol Syndrome
Fetal alcohol syndrome is a condition in which maternal drinking during pregnancy injures the brain of the developing fetus. Alcohol is the most common cause of injury to the fetal brain. Children born with fetal alcohol syndrome may have cognitive impairments and difficulty regulating their behavior. They often have difficulty in school and exhibit behavioral problems, such as impulsiveness, later in life.
The syndrome is estimated to occur in approximately one in every 1,000 births in Western countries. Milder forms of the condition, known as fetal alcohol spectrum disorders, occur more frequently.
Maternal drinking lowers the blood pH of both the mother and the fetus, making the blood more acidic. The researchers hypothesized that this acidity damages the Purkinje cells of the fetal cerebellum. Using 56 pregnant sheep, they induced the change in pH in some sheep using alcohol, while in others they manipulated the extracellular pH. This approach allowed them to test their hypothesis that it was the fall in pH that created the damage, not the alcohol, per se.
Alcohol produced a 45% reduction in Purkinje cells of the fetal cerebellum, while the pH changes alone produced a 24% decrease. A drop in the number of Purkinje cells in the cerebellum is a measure of damage.
However, when the researchers used a drug, doxapram, to block the TASK channels leading into the Purkinje cells, they prevented the change in pH in the fetal cerebellar cells and prevented any reduction in the number of these cells.
"This study demonstrates that direct pharmacological blockade of TASK 1 and TASK 3 channels protects the most sensitive target of fetal alcohol exposure, cerebellar Purkinje cells," the authors concluded.
Finding adds to growing body of work
This study complements work by other researchers who have found success with supplements such as choline, a precursor for the neurotransmitter acetylcholine. These supplements may work on the same mechanism that Dr. Cudd's lab has been researching.
Editor's Notes: To arrange an interview with Dr. Cudd, please contact Christine Guilfoy at firstname.lastname@example.org or (301) 634-7253.
A fuller audio interview with Drs. Cudd and Ramadoss is available in Episode 12 of the APS podcast, Life Lines, at www.lifelines.tv.
Funding: The research was funded by the National Institutes of Health (NIH) Pediatrics Initiatives and the NIH National Institute on Alcohol Abuse and Alcoholism.
Physiology is the study of how molecules, cells, tissues and organs function to create health or disease. The American Physiological Society (APS) has been an integral part of this scientific discovery process since it was established in 1887.