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Neurochemical Changes Following a Single Dose Polybrominated Diphenyl Ether 47 in Mice
Citation:
GEE, J. R., V. C. MOSER, K. MCDANIEL, AND D. W. HERR. Neurochemical Changes Following a Single Dose Polybrominated Diphenyl Ether 47 in Mice. DRUG AND CHEMICAL TOXICOLOGY. Marcel Dekker Incorporated, New York, NY, 34(2):213-219, (2011).
Impact/Purpose:
Previous studies in our laboratory, and in the literature, have shown that exposure to a specific PBDE congener (PBDE 47) during a critical period of brain development may lead to developmental delays and hyperactivity in adulthood.
Description:
Polybrominated diphenyl ethers (PBDEs) are commonly used as commercial flame retardants in a variety of products including plastics and textiles. Previous studies in our laboratory, and in the literature, have shown that exposure to a specific PBDE congener (PBDE 47) during a critical period of brain development may lead to developmental delays and hyperactivity in adulthood. To date the underlying causes of these behavioral alterations are unknown, although in vitro studies have linked PBDEs with potential alterations in neurotransmitter levels, particularly acetylcholine and dopamine. Alterations in dopamine function have also been noted in cases of hyperactivity in rodents and humans. The current study examined monoamine levels in male and female mice acutely exposed with corn oil vehicle or PBDE 47 (1, 10, or 30 mg/kg) on postnatal day (PND) 10. Animals were sacrificed on PND 15, PND 20, and in adulthood (131-159 days old; males only). The cortex, striatum, and cerebellum were isolated and subjected to HPLC analysis to determine the concentration of monoamines within each region. Studies with RT-PCR examined potential changes in expression of the D2 receptor and VMAT mRNA in female mice at PND 15 and 20. In males, a statistically significant increase in dopamine levels was seen within the cortex, regardless of age, but only in the 10 mg/kg PBDE treatment group. On the other hand, female mice showed transiently decreased striatal dopamine, HVA, and DOPAC only at the lowest dose, and a persistent but small decrease in serotonin at the middle dose. There were no significant changes in D2 or VMAT expression. Thus, early developmental exposure to PBDE 47 alters the level of cortical dopamine in male mice (which may correlate with previously reported non-monotonic behavioral observations in littermates) and striatal dopamine and metabolites, and serotonin, in female mice.
