Nicotine & its metabolites: apoptosis in developing neurons
Initial Award Abstract
Smoking is a chronic condition that affects more than 46 million Americans. People who smoke are at risk of heart disease, cancer, and other tobacco-related illnesses that cost more than $50 billion annually to treat, and an additional $47 billion in indirect costs from lost time at work and disability. Cigarette smoking during pregnancy not only damages the health of the smoker, increases the incidence of spontaneous abortion and low birth weight, but also causes long lasting effect such as learning disabilities and hyperactivity in the offspring. Even though the rate of smoking in pregnant women is much lower than the general population in the United States, there were still over 400,000 women who smoked during their pregnancy in 1996, endangering their own health and that of their children. This number will possibly increase in the years to come due to the increasing smoking rate among teenage girls and young women. This is also an important problem in the rapidly growing state of California.
How nicotine affects the health of the fetus is a question that remains to be answered. We hypothesize that nicotine exposure during pregnancy can enhance a cell suicide program, called apoptosis, in developing neuronal cells of the fetus. The purpose of this proposal is to understand whether immature neurons in fetus are more sensitive to nicotine treatment as compare to mature neurons in adults; how the neurons commit to apoptosis after nicotine exposure; and whether we can use apoptosis inhibitors to stop this process. We will also study whether nicotine itself is the most potent reagent causing the neuron damage, or if nicotine metabolites, the products generated in human body from nicotine after its consumption, can also harm neurons. Finding from this study will provide information for the future scientific research on the long-term effect of maternal smoking on the offspring. The results can be also applied to educational efforts for the general public and pregnant women to stop smoking. |