One of the-central issues in neurobiology revolves around the importance of trophic molecules in the survival and-differentiation of dopamine neurons during development and after injury. Moreover, the absence or loss of growth factors has been implicated as a possible cause for a) the degeneration of neurons that occurs in a number of neurodegenerative diseases like Parkinson's and b) the failure of implanted brain cells to survive in transplant therapy. The research proposed in this application examines the role of growth substances (EGF, aFGF, bFGF, TGFB, CNTF, LIF, IL1, NGF, IGF, GMI) in regulating the survival and biochemical differentiation of dopamine neurons deriving development, after damage, and following transplantation. The primary model to be used in these studies was recently developed wherein populations of nearly pure dopamine neurons are isolated for study. This is accomplished by flow cytometry of neurons previously labeled with retrogradely transported fluorescent dyes (diL). Until now, dopamine neurons have comprised only a small (<1%) fraction of midbrain cells used in these studies. With this new found ability to isolate nearly purified (>90%) dopamine neurons, the principal investigator is now in an ideal position to examine the relative contributions made directly by dopamine neurons or indirectly by other cell types and/or their molecular products (ie. trophic factors).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
James A. Shannon Director's Award (R55)
Project #
2R55NS032519-04A1
Application #
2871204
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Oliver, Eugene J
Project Start
1994-08-01
Project End
1998-11-10
Budget Start
1998-09-15
Budget End
1998-11-10
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Biology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
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Bennett, Lori B; Cai, Jingli; Enikolopov, Grigori et al. (2010) Heterotopically transplanted CVO neural stem cells generate neurons and migrate with SVZ cells in the adult mouse brain. Neurosci Lett 475:1-6
Cai, Jingli; Donaldson, Angela; Yang, Ming et al. (2009) The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson's disease model. Stem Cells 27:220-9
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