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).
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