• Mailman, Richard (PI)
  • Krigman, Martin (PI)
  • Goodrum, Jeffrey (PI)
  • Morell, Pierre (PI)
  • Suzuki, Kinuko (PI)
  • Bouldin, Thomas (PI)
  • Krigman, Martin (PI)

Project: Research project


Many environmentally important pollutants, including certain metals and their
organic derivatives are neurotoxic. The development of the nervous system is
influenced by extrinsic factors, and the perturbations caused by toxic metals
often may be different in the developing nervous system than in the mature
nervous system. We have previously demonstrated that lead has unique
intoxicating effects in the immature nervous system: a persistent abnormal
polydipsia to lithium of central nervous system origin; a defect in
synaptogenesis lasting to senescence; and a persistent reduction in myelin. We will continue to utilize a multidisciplinary approach to ellucidate the
neurotoxic effects of heavy metals, to investigate how such neurotoxic
alterations affect the subsequent structural, chemical and functional
development of the nervous system, and to determine the mechanisms of the
neurotoxic action of selective toxic metals. A selected series of organometal
derivatives will be used to investigate structure-neurotoxicity relationships.
These studies will be pursued by investigating the uptake, distribution and fate
of the neurotoxins and by determining the effect of these agents on the
development and stability of neurotransmitter systems, axonal transport and
myelination, and selected aspects of transport systems of the blood-brain
barrier. Emphasis will be placed on those animal and in vitro models which most
directly allow testing of the hypotheses that the developing nervous system is
more sensitive to these agents and that consequences of such perturbations of
neural development may be unique or tardive in their manifestations. Consistent with this, selected aspects of lead neurotoxicity will be
investigated further. In addition, new studies will be pursued based upon our
Program experience, especially those which offer rational comparisons with our
earlier studies with lead. In this regard, initial plans call for examination
of a selected series of organotin compounds and organolead compounds.
Effective start/end date5/1/759/19/98


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $1,024,377.00


Environmental Pollutants
Nervous System
Organotin Compounds
Toxic Actions
Axonal Transport
Myelin Sheath
Heavy Metals
Neurotransmitter Agents
Central Nervous System