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 #
2R01ES002011-09
Application #
3249657
Study Section
Toxicology Study Section (TOX)
Project Start
1978-12-05
Project End
1990-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
9
Fiscal Year
1987
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
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
Granholm, A C; Palmer, M R (1988) Electrophysiological effects of norepinephrine on Purkinje neurons in intraocular cerebellar grafts: alpha- vs beta-specificity. Brain Res 459:256-64
Hoffer, B; Bickford-Wimer, P; Bygdeman, M et al. (1988) Electrophysiological studies of human cerebral and cerebellar cortical tissue grafted to the anterior eye chamber of athymic rodents. Prog Brain Res 78:591-7
Henschen, A; Palmer, M; Verhofstad, A et al. (1988) Intraocular spinal cord grafts: a model system for morphological and functional studies of spinal regeneration. Prog Brain Res 78:187-91
Henschen, A; Hokfelt, T; Elde, R et al. (1988) Expression of eight neuropeptides in intraocular spinal cord grafts: organotypical and disturbed patterns as evidenced by immunohistochemistry. Neuroscience 26:193-213

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