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Effects of Maternal Exposure to Polychlorinated Biphenyls on Notch Signaling in the Fetal Rat BrainEPA Grant Number: U916010
Title: Effects of Maternal Exposure to Polychlorinated Biphenyls on Notch Signaling in the Fetal Rat Brain
Investigators: Herzig, Carolyn T.A.
Institution: University of Massachusetts - Amherst
EPA Project Officer: Just, Theodore J.
Project Period: January 1, 2001 through January 1, 2003
Project Amount: $57,532
RFA: STAR Graduate Fellowships (2001) RFA Text | Recipients Lists
Research Category: Fellowship - Toxicology , Academic Fellowships , Health Effects
The objective of this research project is to determine the effects of maternal exposure to polychlorinated biphenyls (PCBs) on Notch signaling in the fetal rat brain.Approach:
PCBs are industrial chemicals that have neurotoxic effects, and studies indicate that they interfere with normal functions of the endocrine system. Although the manufacturing of PCBs was banned in the 1970s, they remain a major contaminant of the environment and of human tissues. Epidemiological studies show that exposure to PCBs during intrauterine development is highly associated with measurable neurological deficits in the offspring. In addition, deficits associated with PCBs are inversely associated with maternal thyroid hormone (TH) levels. This suggests that PCBs interfere with TH action in the fetal brain. Using in situ hybridization to measure HES-1 and HES-5 mRNA (direct markers of Notch activity), our laboratory has found that both maternal thyroid status and maternal exposure to PCBs influences Notch signaling in the fetal rat brain. We found that Aroclor 1254 produces a dose-dependent increase in HES-1 expression in the ventricular zone. Recent evidence suggests that Notch signaling enhances radial glial cell generation by cortical stem cells at the expense of forming neurons. Our results suggest that PCB exposure may result in a shift toward the production of more glia and fewer neurons in the early cortex.Supplemental Keywords:
fellowship, polychlorinated biphenyls, PCBs, thyroid hormone levels, Notch signaling, contaminants, exposure, neurological deficits, Aroclor 1254.