UCI Study With Rats Shows Why Nicotine Affects Auditory Processing In The Brain
Scientists know that children of women who smoke during pregnancy can develop hearing-related cognitive deficits. For the first time, researchers believe they have evidence that not only implicates nicotine as the culprit, but also shows what the subst
Scientists know that children of women who smoke during pregnancy can develop hearing-related cognitive deficits. For the first time, researchers believe they have evidence that not only implicates nicotine as the culprit, but also shows what the substance does to the brain to cause these deficits.
In a study using rats, Raju Metherate, associate professor of neurobiology and behavior, and colleagues from UC Irvine, showed that nicotine exposure during the equivalent of a human's third trimester led to hearing-related cognitive problems. This is the first time a study has demonstrated this causal link. Further tests then revealed that the probable cause of the deficits was damage to the receptors in the brain that are sensitive to nicotine, which seems to occur when humans or animals are exposed to the substance during development. The study appears this week in the early online issue of the European Journal of Neuroscience.
Children with auditory processing deficits can have a number of hearing-related problems. They may have difficulty understanding speech in a noisy environment, not understand information that is presented verbally, and may not be able to tell the difference between similar sounds.
"This study is significant because it suggests to us precisely what aspect of smoking is so harmful in pregnancy when it comes to cognitive hearing deficits," Metherate said. "Most women who smoke find it difficult to quit during pregnancy. For them, doctors often prescribe a nicotine patch. While that does protect the fetus from the well-known physical under-development related to harmful chemicals in cigarette smoke, exposure to nicotine appears to be enough to cause serious problems on its own, in terms of brain development."
Chemicals known as neurotransmitters act as message carriers between cells and bind with receptors on the cells' surfaces, much like a key fits into the lock. If the receptors are damaged, they can no longer bind properly with the neurotransmitter. Nicotine shares a receptor with the neurotransmitter acetylcholine, which is important for a number of cognitive functions.
Researchers believe that when people are paying attention to something, such as an important sound, acetylcholine is released into the brain. It then interacts with the nicotinic-acetylcholine receptor and, the UCI study showed, thereby enhances sensitivity to that sound. If that receptor is damaged due to prenatal exposure to nicotine, acetylcholine cannot bind with it and increased sensitivity to the important sound is lost.
"While verbal function cannot be measured in an animal, this establishment of a causal relationship between prenatal nicotine exposure and auditory-cognitive deficits is an important step forward in reinforcing these previous findings in humans," Metherate said.
According to the researchers, given the importance of acetylcholine to a number of brain functions, a loss of nicotinic-acetylcholine receptors may have a negative effect on other higher cognitive functions and may also impair vision and other senses.
Nicotine does seem to actually enhance cognitive processing when administered to adults, a finding that has also been shown in previous studies. The researchers found that in this study, nicotine appeared to enhance auditory function in the adult rats, but only if they had not been exposed to the substance during development.
Researchers placed electrodes in the animals' auditory cortex, then exposed them to different frequencies of sound. They found that nicotine made the cortex much more responsive to sound if the rats had not had exposure to nicotine during their early development. In the case of previous exposure, there was no increased sensitivity to sound. According to Metherate, this occurs most likely because the nicotine is mimicking the action of acetylcholine on their shared receptors and increasing responsiveness to sound if those receptors had not been previously damaged.
Collaborators on this study from UCI were Norman Weinberger, research professor of neurobiology and behavior; Frances Leslie, professor of pharmacology; Kevin Liang, graduate student researcher in neurobiology and behavior; Bonnie Sue Poytress, laboratory assistant in neurobiology and behavior; and Yiling Chen, associate specialist in pharmacology. The study was funded by the National Institute on Drug Abuse and the National Institute on Deafness and Other Communication Disorders, both parts of the National Institutes of Health.
About the Study: In the study, the researchers treated one group of one-week-old rats with nicotine and another group with saline, for five consecutive days. One week after birth, rats are in the same developmental stage as a human fetus in the third trimester. Two months later, as adults, the rats were placed in a two-chamber box and taught to cross from one chamber to the other during a five-second tone in order to avoid a shock. Researchers found that after four days of training, the animals treated with saline moved to the other chamber in most of the trials. By contrast, the rats treated with nicotine avoided the shock on significantly fewer trials. Some animals never learned to correlate the tone with the coming shock. Tests showed that the animals did not have a hearing problem -- they could hear the tone, but could not always relate it to the expected behavior -- in this case, moving to a different chamber to avoid the shock. Additional tests to determine the nature of the underlying problem were performed by placing electrodes in the animals' auditory cortex to record brain activity, and showed that the nicotinic-acetylcholine receptor did not function properly.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.3 billion.
Contact: Farnaz Khadem