The response of mesencephalic dopamine neurons in culture to growth factors: Effects on development and neurotoxicity.
Item
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Title
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The response of mesencephalic dopamine neurons in culture to growth factors: Effects on development and neurotoxicity.
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Identifier
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AAI9707105
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identifier
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9707105
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Creator
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Hou, Jyh-Gong Gabriel.
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Contributor
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Adviser: Catherine Mytilineou
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Date
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1996
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience | Biology, Cell
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Abstract
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Parkinson's disease is characterized by dopaminergic neuronal degeneration in the substantia nigra. Several peptide neurotrophic factors have been shown to be able to maintain the survival and promote the recovery of injured dopaminergic neurons. I investigated the effects of two trophic factors, glial cell line-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF). bFGF is an astroglial cell mitogen while GDNF is not, although it is secreted by glial cells. By using the experimental model of rat embryonic mesencephalic cultures, I tested whether or not these growth factors could modify the damage caused by the specific dopaminergic neurotoxins 1-methyl-4-phenylpyridinium (MPP{dollar}\sp+{dollar}) and 6-hydroxydopamine (6-OHDA) and help neurons recover following toxin-induced damage.;My results show that GDNF supports the growth of normally developing dopaminergic neurons without affecting glial proliferation. GDNF is unable to prevent the toxicity of MPP{dollar}\sp+{dollar} or 6-OHDA, but it stimulates the survival and recovery of dopaminergic neurons after damage by MPP{dollar}\sp+{dollar}. bFGF also supports the development of dopaminergic neurons. This effect is mediated through astroglial cells but is not due to secretion of GDNF by the stimulated glia. Like GDNF, bFGF does not prevent MPP{dollar}\sp+{dollar} damage to the cultured neurons but effectively protects from 6-OHDA toxicity. This protection is again mediated by glial cells. bFGF-treated mesencephalic cultures have higher levels of reduced glutathione (GSH). Following 6-OHDA treatment GSH levels are further increased. The bFGF effects on GSH are also mediated by glia. Protection from 6-OHDA by bFGF is diminished when GSH levels in mesencephalic cultures are decreased by the GSH synthesis inhibitor L-buthionine sulfoximine (L-BSO).;Astrocytic glial cells synthesize and secrete factors such as GDNF to enhance the development and survival of dopaminergic neurons in vitro. The stimulation of glial cells by bFGF allows the upregulation of the antioxidant mechanisms to help cell survival after oxidative stress damage. The role of these neurotrophic factors may be significant for the clinical treatment of Parkinson's disease in the future.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
