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Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

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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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Author notes

  1. R. M. Booze

    Present address: Dept. Physiology and Pharmacology, Bowman Gray School of Medicine, 27103, Winston-Salem, NC

  2. C. F. Mactutus

    Present address: , 1905 Winding Ridge Rd., 27127, Winston-Salem, NC

Authors and Affiliations

  1. Division of Toxicology, Department of Environmental Health Sciences, The Johns Hopkins University, 21205, Baltimore, Maryland, USA

    R. M. Booze

  2. Developmental Neurobiology Group, Laboratory of Behavioral and Neurological Toxicology, National Institute of Environmental Health Sciences, 27709, Research Triangle Park, North Carolina, USA

    C. F. Mactutus

Authors
  1. R. M. Booze
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  2. C. F. Mactutus
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Booze, R.M., Mactutus, C.F. Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats. Experientia 46, 292–297 (1990). https://doi.org/10.1007/BF01951770

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  • DOI: https://doi.org/10.1007/BF01951770

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