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The study, reported in the on line, Early Edition
of Proceedings of the National Academy of Sciences the week of April
23-27, showed that the toxicant altered the rat pups’ auditory cortex,
the part of the brain that processes sound. The neural circuitry of
this region was disorganized and the nerve cells had a decreased
capacity to change, or "learn," in response to sound. The capacity of
the brain’s cortex to change in response to stimuli contributes to the
progressive development of cognitive function.
In children with a variety of developmental
disorders, including language impairments and autism, the auditory
cortex responds abnormally to sound. Some scientists believe this is
the basis of the conditions.
While the scientists emphasized that their finding
did not demonstrate that the toxicant causes developmental disorders,
they said that, given its severe impact in the rat pups and the
prevalence of this class of PCB in the environment - known as
non-coplanar PCBs - and related chemicals warrant serious attention.
"The study indicates that there are chemicals out
there, this being just one example, that could profoundly affect
development," says Tal Kenet, PhD, who led the research while a
postdoctoral fellow in the lab of senior author Michael Merzenich, PhD,
UCSF Francis A. Sooy Professor of Otolaryngology and a member of the
Keck Center for Integrative Neuroscience at University of California,
San Francisco.
"This is a red flag," says Merzenich. "The impact
of this class of chemicals, whose toxicity has been under-appreciated,
must be studied in human populations, and fast."
The finding builds on recent cell culture studies
by co-author Isaac Pessah, PhD, professor of molecular biosciences at
University of California, Davis, showing that non-coplanar PCBs
significantly influence chemical and electrical signaling between
neurons that affects brain development and learning.
While developmental disorders have a strong genetic
component, many scientists, including the authors, believe that, in
some circumstances the disorders are only expressed when environmental
factors act upon inherited mutated genes.
"We know that some environmental risk applies in
the early developmental history of the brain in the fetus and baby,"
says Merzenich, a pioneer of studies on the neural basis of learning
and memory and the neural origin of developmental disorders.
"People have struggled with what kinds of factors
these might be. I think environmental poisons, including the chemical
we’ve examined in this study, are very good candidates."
Given that the rat pups in the study did not have a
genetic susceptibility to a developmental disorder, the scientists
suspect that the vulnerability might be greater in genetically
susceptible human populations.
The study did not attempt to distinguish whether
the PCB affected the rat pups’ developing brains while they were
gestating or while they were nursing, but scientists reported in 2003
that infants who were breast fed for more than three months had 6.6
times higher levels of PCBs in their blood plasma than infants who did
not breast feed.
This finding, coupled with other factors -
particularly an increase in the rate and duration of breast feeding in
the United States, epidemiologic evidence of negative effects on
cognitive function in children, and lab evidence in rats, following
PCB exposure in high-risk environments - is noteworthy, says Kenet,
who is now a junior faculty member at Harvard Medical School and
Massachusetts General Hospital.
"Breast feeding is by far the optimal choice for
the vast majority of infants, given its indisputable nutritional and
immunological benefits," says Kenet, "and our findings, conducted in
rats, by no means suggest women should alter their nursing practice.
The finding does suggest the need for studies in human populations to
determine whether there are possible risks associated with breast
feeding in cases of extreme exposure to this class of chemicals, in
particular in infants who may have a genetic predisposition to
developmental disorders based on their family history."
Polychlorinated biphenyls (PCBs), used mostly as
coolants and lubricants beginning in the 1930s, were banned in 1977.
Early toxicology studies focused mostly on a subset of PCBs known as
coplanar PCBs, which were shown in cell culture and animal models to
pose a serious health risk. Recent studies, however, have shown that
non-coplanar PCBs are particularly stable, are less susceptible to
degradation by organisms in the environment, and predominate in
environmental and human tissue samples over their counterparts.
In the current study, the scientists focused on a
non-coplanar PCB known as PCB95, which is prevalent in the environment,
and has qualities that could make it among the more hazardous.
In the primary experiment, one set of adult rats
was exposed to the toxicant in their food during pregnancy and during
the first three weeks after giving birth, when they nursed their pups.
Another group was fed normally. After both sets of pups had been
weaned, the researchers recorded the electrical activity of neurons in
their primary auditory cortex, the first sensory region to develop in
the cortex.
The results were dramatic, says Kenet. While the
brain region of the pups raised without exposure to the toxicant was
developing typically, the brain region in the pups exposed to the
toxicant in utero and while nursing was profoundly altered.
"The animals could hear, but their brain’s
representation of what they heard was grossly disturbed," says
Merzenich.
In one pronounced change, the balance of inhibitory
and excitatory signaling between nerve cells, which contributes to the
appropriately controlled responses of the brain to stimuli, was
disrupted. Strong evidence indicates that there is imbalance in
signaling throughout the brain of children with some developmental
disorders, such as autism, says Merzenich.
In a secondary experiment, the toxicant-exposed
pups were raised in a modified sound environment in which they were
exposed to continuous tone or noise pulses. It was here that the
auditory cortex’s decreased capacity to change in response to sound
was revealed. "This activity is crucial in the developing brain," says
Merzenich. "Interruptions in these early-learning progressions
contribute to learning-related challenges."
As the auditory cortex is the first sensory region
to develop, its abnormal development in the rat pups could be just a
hint of more pervasive effects of exposure, the scientists say.
PCB95 is closely related in its chemical structure
to polybrominated diphenyl ether (PBDE), which is difficult to study
and has only begun to receive attention for its environmental effects,
says Kenet. It has been used in large quantities in the last 25 years,
mostly in fire retardation in home and office furniture and
electronics.
"We’ve done as yet unpublished studies with PDBEs,"
says Pessah, director of the UC Davis Center for Children's
Environmental Health. "The current finding could be just the tip of
the iceberg." |
