Abstract

Recent studies of fetal transplants containing cholinergic nerve cells of the rat septal nucleus have shown that the transplants have the capacity to innervate the hippocampal formation of recipient rats. The pattern of reinnervation appears to be quite specific and mimics the pattern produced by intrinsic septal afferents. Electrophysiological studies suggest that the transplant-derived innervation forms functional connections. This notion is further supported by behavioral studies that have demonstrated a recovery of maze learning abilities by rats with septal tissue transplanted into the denervated hippocampal formation. These studies in conjunction with other transplantation studies have led to the proposed use of neural transplants in the treatment of neurological disorders that stem from the degeneration specific neuronal populations. We propose to determine whether alternate sources of cholinergic nerve cells from the peripheral and central nervous system can innervate the hippocampal formation and form functional connections. Ciliary ganglia, ventral spinal cord, and basal nuclei from fetal rats; and ciliary ganglia and basal nuclei from adult rats will be grafted or implanted as cell suspensions into the hippocampal formation of adult rats. Evidence for the cholinergic innervation of the hippocampus will be obtained from histochemical methods to reveal acetycholinesterase and choline acetyltransferase localization and from assays to determine choline acetyltransferase activity. The functional nature of the transplant-derived innervation will be assessed by electrically stimulating the transplant and recording the evoked responses within the hippocampal formation, and by analyzing the slow- wave activity in behaving animals. Recovery of behavioral function will be determined by assessing the T-maze and water maze learning abilities of rats with and without transplants. These studies will determine whether alternate sources of cholinergic nerve cells can innervate target sites in the host hippocampal formation and restore functions normally mediated by cholinergic septal fibers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024464-02
Application #
3409129
Study Section
Neurology A Study Section (NEUA)
Project Start
1987-09-01
Project End
1989-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Indiana University-Purdue University at Indianapolis
Department
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202

  Publications

Duan, W M; Westerman, M; Flores, T et al. (2001) Survival of intrastriatal xenografts of ventral mesencephalic dopamine neurons from MHC-deficient mice to adult rats. Exp Neurol 167:108-17
Duan, W M; Zhao, L R; Westerman, M et al. (2000) Enhancement of nigral graft survival in rat brain with the systemic administration of synthetic fibronectin peptide V. Neuroscience 100:521-30
Rodrigues, C M; Stieers, C L; Keene, C D et al. (2000) Tauroursodeoxycholic acid partially prevents apoptosis induced by 3-nitropropionic acid: evidence for a mitochondrial pathway independent of the permeability transition. J Neurochem 75:2368-79
Wallenfriedman, M A; Conrad, J A; DelaBarre, L et al. (1999) Effects of continuous localized infusion of granulocyte-macrophage colony-stimulating factor and inoculations of irradiated glioma cells on tumor regression. J Neurosurg 90:1064-71
Pundt, L L; Jorn, E A; Conrad, J A et al. (1997) Organization and histochemical phenotype of human fetal cerebellar cells following transplantation into the cerebellum of nude mice. Cell Transplant 6:479-89
Pundt, L L; Narang, N; Kondoh, T et al. (1997) Localization of dopamine receptors and associated mRNA in transplants of human fetal striatal tissue in rodents with experimental Huntington's disease. Neurosci Res 27:305-15
Li, Y J; Low, W C (1997) Intra-retrosplenial cortical grafts of cholinergic neurons: functional incorporation and restoration of high affinity choline uptake. Neurochem Res 22:589-95
Li, Y J; Low, W C (1997) Intraretrosplenial cortical grafts of fetal cholinergic neurons and the restoration of spatial memory function. Cell Transplant 6:85-93
Jansen, E M; Solberg, L; Underhill, S et al. (1997) Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats. Exp Neurol 147:487-97
Jansen, E M; Low, W C (1996) Quantitative analysis of contralateral hemisphere hypertrophy and sensorimotor performance in adult rats following unilateral neonatal ischemic-hypoxic brain injury. Brain Res 708:93-9

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