Nicotine Exposure During Fetal Development Leads To
Hearing Problems
Editor: Scientists at the University of California at Irvine believe they
have discovered how nicotine exposure during development leads to hearing
loss in the developing fetus. Here's the press release.
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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.
