Abstract

This project will examine the effects of low-level chronic perinatal and acute lead exposure on the histological organization and electrophysiological function in a number of central nervous areas. Experiments will be conducted in brain grafts and brain slices in vivo, as well as in the intact animals. Other heavy metal toxicants, such as cadmium, mercury, and thallium, will also be examined. The techniques to be employed include histological and histochemical staining to localize various transmitter-containing cells and fibers, extracellular and intracellular recordings from single neurons, and local drug administration using multibarreled micropipettes. By determining any lead-induced alterations in histological and electrophysiological organization of brain areas, and comparing the vulnerability of developing versus mature central nervous system, we hope to define more precisely the potential hazards of low-level lead exposure. Moreover, the comparison of such changes in isolated versus intact central nervous sytems should provide insights into the mechanisms of any heavy metal-induced disturbances.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES002011-11
Application #
3249661
Study Section
Toxicology Study Section (TOX)
Project Start
1978-12-05
Project End
1991-07-31
Budget Start
1989-08-01
Budget End
1991-07-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Inoue, H K; Henschen, A; Olson, L (1994) Human fetal spinal cord xenografted to the eye of athymic nude rats: survival, ultrastructural differentiation, glial responses and vascular interactions. J Electron Microsc (Tokyo) 43:1-9
Luthman, J; Oskarsson, A; Olson, L et al. (1992) Postnatal lead exposure affects motor skills and exploratory behavior in rats. Environ Res 58:236-52
Luthman, J; Olson, L; Bjorklund, H et al. (1991) Combined lead acetate and disulfiram treatment-induced alterations of glial fibrillary acidic protein (GFA) immunoreactive astrocytes in brain smears. Toxicology 65:333-46
Henschen, A; Goldstein, M (1990) Expression of tyrosine hydroxylase-like immunoreactivity in cell bodies in intraocular spinal cord grafts: a comparison with classical Falck-Hillarp histochemistry. J Chem Neuroanat 3:77-83
Eriksdotter-Nilsson, M; Gerhardt, G; Seiger, A et al. (1989) Age-related alterations in noradrenergic input to the hippocampal formation: structural and functional studies in intraocular transplants. Brain Res 478:269-80
Inoue, H K; Henschen, A; Olson, L (1988) Ultrastructure of spinal cord grafts with and without cografts of locus coeruleus in oculo. Exp Neurol 102:109-20
Henschen, A F; Goldstein, M; Palmer, M R (1988) Evidence for functional contact between cografted locus coeruleus and spinal cord in oculo: electrophysiological studies. Brain Res 474:66-74
Seiger, A; Bygdeman, M; Goldstein, M et al. (1988) Human fetal catecholamine-containing tissues grafted intraocularly and intracranially to immuno-compromised rodent hosts. Prog Brain Res 78:449-55
Miller, J A; Hoffer, B J; Zahniser, N R (1988) An improved calibration procedure for computer-based quantitative autoradiography utilizing a mathematical model for the non-linear response of camera and film. J Neurosci Methods 22:233-8
Granholm, A C; Gerhardt, G A; Moore, E et al. (1988) Toluene exposure during maturation of intraocular brain tissue transplants: alterations of host and graft cerebellar Purkinje neuron function and sensitivity to norepinephrine. Toxicol Appl Pharmacol 96:296-304

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