Transplantation of neural cell between different species may lead to a clinically beneficial therapy for certain neurological disease such as Alzheimer's dementia or neurological deficits due to aging. In order to determine the usefulness of the procedure, the characteristics of the transplant need to be explained and the role which the transplant plays in the recovery process needs to be determined both in young and old animals. The present experiments are designed to determine if the transplant plays in the recovery of function in young and old animals, even if the transplant survives for only a few months and to analyze the ability of the transplant to make connections between the transplant and the host. Because such cross-species transplants do not survive well in the host, the y present the best, and perhaps the only model for determining if the beneficial effects of the transplant can be assessed after the useful life of the transplant, i.e., do the beneficial effects of the transplant continue after the transplant itself dies and will the response change in old animals. Cholinergically denervating the rat hippocampus creates a behavioral deficit that can be shown by the rats inability to learn a rewarded alternation task. The cross-species transplants restore the ability to learn the task.
One specific aim of the experiments is to relate the long term behavioral recovery tot he survival of the transplant.
The second aim i s to begin to determine how the transplanted cells grow into the host. Taking advantage of a label that specifically identifies mouse neurons, the outgrowth of all viable transplanted neurons regardless of transmitter type can be studied. There is an unexplained difference between the outgrowth of species specific fibers and fibers identified by an enzymes used to identify cholinergic fibers. This discrepancy will be clarified. The formation of synapses will also be analyzed as a more direct way of investigating the formation of connections between donor and host. The behavioral test is one method of detecting changes in the function of the system. We will also use the histochemical demonstration of cytochrome oxidase as a relative measure of the physiological activity of hippocampal structures before and after the lesion and transplant.
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| Legendre, D I; Vietje, B P; Wells, J (1994) The differentiation of dentate granule cells following transplantation. Exp Neurol 125:247-57 |
| Farber, S D; Onifer, S M; Kaseda, Y et al. (1988) Neural transplantation of horseradish peroxidase-labeled hippocampal cell suspensions in an experimental model of cerebral ischemia. Prog Brain Res 78:103-7 |
