Duke University Alumni Magazine
pumps to infuse precisely metered doses of a chemical-perhaps nicotine, a pesticide, or some other substance--into the bloodstreams of pregnant rats. Then, using meticulous biological analyses and microscopic studies, they measure the chemical's effects on the brains of the rats' unborn offspring. The techniques have proven to be a powerful approach to pinpointing the effects of nicotine on the growing brain, says Slotkin. "Until such studies, we had only statistical associations of the effects of women smoking during pregnancy on the outcomes of their children. But those kinds of associations didn't automatically connote a causal relationship. The picture was confused by all kinds of other factors in the smoking lifestyle--including lower socioeconomic status, which leads to poor prenatal care, as well as other risky behaviors, including use of other drugs of abuse and alcohol."
With animal research, Slotkin can test individual components of tobacco, determining which actually elicit such effects as brain damage or sensitivity to hypoxia after birth--a condition that can trigger Sudden Infant Death Syndrome (SIDS). Slotkin's studies revealed the damning details of the mechanisms of nicotine's damage to the fetal brain. The experiments showed that nicotine mimics a key brain neurotransmitter, acetylcholine, which is normally released in a precise sequence of signals that tell the sensitive growing brain cells how to "wire" their connections. Nicotine stimulates the same cell receptors as acetylcholine, but at the wrong time and with the wrong intensity, confusing the normal development process and causing the fetal brain to miswire itself permanently. Nicotine also kills brain cells outright by inducing them to "age" prematurely and die. Slotkin's experiments have clearly implicated nicotine as the cause of one-third to two-thirds of cases of SIDS, the second leading cause of infant death after accidents. Nicotine damages the adrenal system, which the infant needs to "alert" its body to stress. The infant uses the adrenal system to boost heart rate and breathing during periods of hypoxia--during birth itself and after birth when some babies have an inherited predisposition to mild apnea, or breathing cessation, during sleep. In the newborn, the heart and respiratory systems are not yet fully wired with nerve cells to allow them to respond to hypoxia, as in adults. Instead, they rely on secretion of certain adrenal stress hormones, called catecholamines. In their experiments, the Duke pharmacologists first infused into pregnant rats doses of nicotine that mimicked blood levels found in typical human smokers. After the baby rats were born, http://www.dukemagazine.duke.edu/alumni/dm17/slotkin.html[1/23/2012 3:14:06 PM]