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Certain PCB's Causes Developmental Abnormalities In Rat Pups

Science Daily — Scientists have determined that a specific class of

PCB causes significant developmental abnormalities in rat pups whose

mothers were exposed to the toxicant in their food during pregnancy

and during the early weeks when the pups were nursing.

This class of PCB traditionally has not been considered particularly

hazardous.

The pups were estimated to have levels of the toxicant in their blood

that were roughly equivalent to those found in the blood of breast fed

babies of mothers exposed to extremely high levels of the toxicant

from contaminated fish, soil, water and air in high-risk environments.

The study, reported in the Proceedings of the National Academy of

Sciences, 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 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, , 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 Center for Children's Environmental Health.

" The current finding could be just the tip of the iceberg. "

Other co-authors of the study were Froemke, PhD, and Christoph

Schreiner, MD, PhD, both of the Keck Center for Integrative

Neuroscience at UCSF.

The study was funded by Cure Autism Now, the UC M.I.N.D.

Institute, the Jane Coffin Childs Foundation for Medical Research, the

Sandler Program in Basic Sciences, the National Institutes of Health

and the Environmental Protection Agency.

Note: This story has been adapted from a news release issued by

University of California - San Francisco.