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PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.
Citation:
White, L. D., T. L. Lassiter, K. P. Das, AND S Barone. PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. Pregnant Long-Evans rats were dosed daily (p.o.) with CPF (0, 3, 5, 7, and 10 mg/kg) in corn oil on gestational days 14-18. Fetuses were examined at 2, 5, 10, and 24 hours after the last dose. Immunohistochemistry showed very little nerve growth factor (NGF) immunoreactivity (IR) in the fetal brain. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) immunohistochemistry of fetal brains showed significant IR in the ventricular and subventricular zones. In addition, BDNF IR was widely and spottily distributed throughout the intermediate zone and cortical plate of the control neocortex. There was a decrease in BDNF and NT-3 IR in the brains of CPF treated fetuses. These CPF-related changes in NTF-IR are consistent with quantitative changes in whole brain BDNF and NT-3 levels determined by enzyme-linked immunoabsobent assays (ELISA)'s. The immunohistochemistry demonstrates that these changes in NTF levels determined in ELISA's are primarily limited to proliferative zones of the forebrain. Results from cell death ELISA showed the highest level of oligonucleosomal at the 7 mg/kg/day dosage at 5 hours after the last dose of CPF. Terminal transferase dUTP nick end-labeling (TUNEL) assays of fetal brains showed increased numbers of apoptotic cells in the proliferative zones of the striatum, hippocampus and cortical plate of the neocortex. This apparent increase in apoptosis is localized primarily to proliferative zones in the striatum and the hippocampus. The altered pattern of apoptosis in the fetal brains of CPF-exposed rats were reciprocal to the changes in BDNF and NT-3 IR in proliferative and post migratory zones. This observed increase in apoptosis could be due to the demonstrated changes in neurotrophin levels. Further, these changes in regional levels of neurotrophins and apoptosis with CPF exposure suggest possible alterations in cell number and function that could persist in the adult nervous system. This abstract does not reflect EPA policy.