NeuroanatomyEnvironmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats
Section snippets
Animal husbandry and Pb2+ analysis
Female Long-Evans rats (225–250 g) were purchased from Charles River, Inc. (Wilmington, MA, USA) and fed 0 or 1500-ppm Pb2+ acetate. The Pb2+ acetate was incorporated into the rat chow mix (RMH 1000) and the food mixture was made into pellets by the manufacturer (Dyets, Bethlehem, PA, USA). Feeding of the Pb2+-containing and control diets was initiated 10 days before breeding females to untreated Long-Evans male rats. Dams were maintained on their respective diets during gestation and
Blood Pb2+ levels
Whole blood Pb2+ concentrations at PN50 were as follows: control (n=15): 0.75±0.11 μg/dL and Pb2+-exposed (n=14): 25.8±1.28 μg/dL. These blood Pb2+ concentrations are similar to our previous studies (Nihei et al., 2000) and are of the same magnitude as those present in certain segments of the population in the United States and throughout the world (Toscano and Guilarte, 2005).
Effect of Pb2+ exposure on cell proliferation and cellular fate
One day after the last BrdU injection, newly generated cells in the dorsal DG of both control and Pb2+-exposed rats
Discussion
The main finding of the present study is that chronic exposure to environmentally relevant levels of Pb2+ during early life alters granule cell neurogenesis and morphology in the DG of young adult rats. We show that Pb2+ exposure decreased the proliferation of newly generated cells but did not alter their cellular fate. Further, it decreased the survival of newly born granule cells and altered their morphology manifested by reductions in the length density of DCX-labeled apical dendrites and in
Conclusion
In summary, chronic exposure to Pb2+, a ubiquitous environmental pollutant and neurotoxicant, has detrimental effects on granule cell proliferation, survival and morphology in the DG altering the cytoarchitecture of the rat hippocampus. These findings provide a cellular and morphological basis for the deficits in hippocampal LTP and spatial learning documented in Pb2+-exposed animals.
Acknowledgments
This work was supported by grant number ES06189 to T.R.G. from the National Institute of Environmental Health Sciences. The authors give thanks to Dr. Mary Blue for assistance with the MicroBrightField Stereology System.
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