Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats |
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Authors: | R M Booze C F Mactutus |
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Institution: | (1) Division of Toxicology, Department of Environmental Health Sciences, The Johns Hopkins University, 21205 Baltimore, Maryland, USA;(2) Developmental Neurobiology Group, Laboratory of Behavioral and Neurological Toxicology, National Institute of Environmental Health Sciences, 27709 Research Triangle Park, North Carolina, USA;(3) Present address: Dept. Physiology and Pharmacology, Bowman Gray School of Medicine, 27103 Winston-Salem, NC;(4) Present address: 1905 Winding Ridge Rd., 27127 Winston-Salem, NC |
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Abstract: | Summary The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS. |
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Keywords: | Triethyl lead development central nervous system neurotoxicity hyperreactivity hippocampus cholinergic rat |
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