The experiments will determine the anatomical and behavioral effects of implantation of embryonic hippocampal and cerebellar tissue into the brains of adult rats with previous toxicant-induced neuropathology. The objectives of this research are to determine whether implantation of embryonic neural tissue is a biologically viable method of alleviating the consequences of toxic damage to the central nervous system.
The specific aims of the research, first, to determine the degree to which behavioral recovery can be produced in rats exposed to a neurotoxin, trimethyltin (TMT), which has a specific toxic effect on the hippocampus, by implantation of embryonic hippocampal tissue. Three behavioral paradigms sensitive both to TMT-induced neuropathology and to hippocampal damage will be used to achieve this aim. These tasks are passive avoidance, an operant task in which low rates of response are reinforced (DRL), and a radial arm maze paradigm. The second specific aim is to study the anatomical development of embryonic hippocampal and cerebellar tissue implanted into the brain of rats suffering from neuropathology produced by exposure to TMT. Accomplishment of this objective will include observation of the histological structure of the TMT-damaged brain, the histological structure of the transplants, the afferent and efferent connections of the TMT-damaged hippocampus, the afferent and efferent connections of the transplanted embryonic tissue after it has developed in the host brain, and the cholinergic and noradrenergic innervation patterns of both the TMT-damaged hippocampus and the developed transplant. The histological structure will be studied using standard Nissl stains. The afferent and efferent connections will be studied using retrograde (horseradish peroxidase) and anterograde (autoradiography) axon tracing techniques. The cholinergic and noradrenergic patterns of innervation will be studied using, respectively, acetylcholinesterase staining and histofluorescent methodology. Completion of these experiments will produce data which will extend knowledge concerning the neuropathological and behavioral sequelae of exposure to a toxic environmental health hazard, trimethyltin, and also provide information regarding the usefulness of neural transplantation technology in alleviating neurotoxicant-produced deficits.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004070-02
Application #
3251934
Study Section
Toxicology Study Section (TOX)
Project Start
1986-06-15
Project End
1989-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
East Tennessee State University
Department
Type
Schools of Medicine
DUNS #
City
Johnson City
State
TN
Country
United States
Zip Code
37614
Freeman 3rd, J N; Baisden, R H; Woodruff, M L (1995) Fetal Ammon's horn transplants improve acquisition of a radial arm maze and a low-rate operant schedule in trimethyltin-treated rats. Cell Transplant 4:113-22
Woodruff, M L; Baisden, R H; Cannon, R L et al. (1994) Effects of trimethyltin on acquisition and reversal of a light-dark discrimination by rats. Physiol Behav 55:1055-61
Cannon, R L; Hoover, D B; Baisden, R H et al. (1994) The effect of time following exposure to trimethyltin (TMT) on cholinergic muscarinic receptor binding in rat hippocampus. Mol Chem Neuropathol 23:47-62
Cannon, R L; Hoover, D B; Baisden, R H et al. (1994) Effects of trimethyltin (TMT) on choline acetyltransferase activity in the rat hippocampus. Influence of dose and time following exposure. Mol Chem Neuropathol 23:27-45
Woodruff, M L; Baisden, R H; Cannon, R L (1993) Transplant-induced working memory deficits in hippocampectomized rats. Physiol Behav 54:579-87
Woodruff, M L; Baisden, R H; Nonneman, A J (1992) Effects of transplantation of fetal hippocampal or hindbrain tissue into the brains of adult rats with hippocampal lesions on water maze acquisition. Behav Neurosci 106:39-50
Cannon, R L; Hoover, D B; Woodruff, M L (1991) Trimethyltin increases choline acetyltransferase in rat hippocampus. Neurotoxicol Teratol 13:241-4
Wray, S; Baisden, R H; Woodruff, M L (1991) Neurochemical anatomy of fetal hippocampus transplanted into large lesion cavities made in the adult rat brain. Exp Neurol 111:36-48
Woodruff, M L; Baisden, R H; Nonneman, A J (1991) Anatomical and behavioral sequelae of fetal brain transplants in rats with trimethyltin-induced neurodegeneration. Neurotoxicology 12:427-44
Woodruff, M L; Baisden, R H (1990) Exposure to trimethyltin significantly enhances acetylcholinesterase staining in the rat dentate gyrus. Neurotoxicol Teratol 12:33-9

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