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.
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