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CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.
Citation:
Gilbert, M. E., M. E. Kelly, S. Salant, AND J. Goodman. CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. Presented at Society for Neuroscience, New Orleans, LA, 11/9-13/2003.
Description:
CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993.
The dentate granule cell (DG) layer of the hippocampus has the distinctive property of ongoing neurogenesis that continues throughout adult life. Although the function of these new neurons and the mechanisms that regulate their birth are unknown, age, activity, diet, psychosocial stress, and NMDA receptor activation have all been demonstrated to regulate this type of neurogenesis. The present study examined the effects of the classic environmental contaminant lead on this process. Pregnant LE rats were exposed to a low level of Pb-acetate (0.2%) via the drinking water from late gestation (GD16) until weaning. On PN-21 half of the Pb-exposed animals were weaned to control drinking water (Wean) and the remainder were maintained on Pb water (Life). Animals were paired housed from weaning and on PN75 were administered a series of injections of a thymidine analog bromodeoxyuridine (BrdU), a marker of DNA synthesis that labels proliferating cells and their progeny. At 12 hr intervals for 12 days, rats received an ip injection of BrdU (50 mg/kg). Subjects were sacrificed and perfused 24 hr and 28 days after the last injection. Immunohistochemistry for the detection of BrdU-labeled cells was performed on 40 m coronal sections throughout the hippocampus. Continuous exposure to Pb (Life) reduced the total number of BrdU-positive cells at 28 days without affecting the total number of labeled cells evident 24 hr after the last injection. No differences in the number of progenitor cells labeled or surviving were seen between control and Wean animals. Double labeling indicated that the BRDU-labeled cells were not GFAP positive, suggesting that the bulk of the surviving cells are of a neuronal not glial phenotype. These data indicate that chronic low level Pb exposure reduces the capacity for neurogenesis in the adult nervous system. (Does not reflect US EPA policy).