Transplantation of embryonic neural tissue to the central nervous system of brain damaged adult host rats has been demonstrated to induce anatomical indices of reinnervation, biochemical indices of neurotransmitter restoration and behavioral indices of functional recovery. Aged rats exhibit specific anatomical, biochemical and behavioral deficits in systems that have been previously demonstrated by this laboratory to respond favorably to transplantation of embryonic neural tissue in the adult host rat. We propose to determine 1) if the aged rat will act as a receptive host of transplanted embryonic neural tissue, and 2) whether the transplants will reverse the behavioral deficits measured. Further experiments will determine 1) the optimal parameters of transplantation, 2) whether transplantation at an earlier date will protect the development of aged related deficits and, 3) whether multiple grafts are more effective than single grafts. Subsequent experiments will test 1) effectiveness of embryonic nerve cells in other brain areas, 2) combined effect of drug treatments and transplants and 3) the effectiveness of cross-species transplantation. We will use histochemical methods to determine the extent of anatomical innervation, biochemical markers as indices of neurotransmitter restoration, and behavioral tests as indices of functional recovery. The overall objective of the research is to introduce the transplantation techniques into the ongoing investigation of aging as a new tool to determine basic mechanisms underlying the aging process.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006088-03
Application #
3116882
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1985-07-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Jessberger, Sebastian; Gage, Fred H (2008) Stem-cell-associated structural and functional plasticity in the aging hippocampus. Psychol Aging 23:684-91
Lein, Edward S; Callaway, Edward M; Albright, Thomas D et al. (2005) Redefining the boundaries of the hippocampal CA2 subfield in the mouse using gene expression and 3-dimensional reconstruction. J Comp Neurol 485:1-10
Pizzo, Donald P; Paban, Veronique; Coufal, Nicole G et al. (2004) Long-term production of choline acetyltransferase in the CNS after transplantation of fibroblasts modified with a regulatable vector. Brain Res Mol Brain Res 126:1-13
Markakis, Eleni A; Palmer, Theo D; Randolph-Moore, Lynne et al. (2004) Novel neuronal phenotypes from neural progenitor cells. J Neurosci 24:2886-97
Lein, Ed S; Zhao, Xinyu; Gage, Fred H (2004) Defining a molecular atlas of the hippocampus using DNA microarrays and high-throughput in situ hybridization. J Neurosci 24:3879-89
Klassen, Henry; Imfeld, Karen L; Ray, Jasodhara et al. (2003) The immunological properties of adult hippocampal progenitor cells. Vision Res 43:947-56
Rhodes, Justin S; van Praag, Henriette; Jeffrey, Susan et al. (2003) Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behav Neurosci 117:1006-16
Vallieres, Luc; Campbell, Iain L; Gage, Fred H et al. (2002) Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci 22:486-92
Zhao, X; Lein, E S; He, A et al. (2001) Transcriptional profiling reveals strict boundaries between hippocampal subregions. J Comp Neurol 441:187-96
Palmer, T D; Willhoite, A R; Gage, F H (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479-94

Showing the most recent 10 out of 71 publications