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Neuronal degeneration is accompanied by primarily oligodendrocytic accumulation of \u03b1-synuclein (\u03b1syn) as opposed to the neuronal inclusions more commonly found in other \u03b1-synucleinopathies such as Parkinson's disease. It is unclear how \u03b1syn accumulation in oligodendrocytes may lead to the extensive neurodegeneration observed in MSA; we hypothesize that the altered expression of oligodendrocyte-derived neurotrophic factors by \u03b1syn may be involved. In this context, the expression of a number neurotrophic factors reportedly expressed by oligodendrocytes [glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor 1 (IGF-1), as well as basic fibroblast growth factor 2 (bFGF2), reportedly astrocyte derived] were examined in transgenic mouse models expressing human \u03b1syn (h\u03b1syn) under the control of either neuronal (PDGF\u03b2 or mThy1) or oligodendrocytic (MBP) promoters. Although protein levels of BDNF and IGF-1 were altered in all the \u03b1syn transgenic mice regardless of promoter type, a specific decrease in GDNF protein expression was observed in the MBP-h\u03b1syn transgenic mice. Intracerebroventricular infusion of GDNF improved behavioral deficits and ameliorated neurodegenerative pathology in the MBP-h\u03b1syn transgenic mice. Consistent with the studies in the MBP-h\u03b1syn transgenic mice, analysis of GDNF expression levels in human MSA samples demonstrated a decrease in the white frontal cortex and to a lesser degree in the cerebellum compared with controls. These results suggest a mechanism in which \u03b1syn expression in oligodendrocytes impacts on the trophic support provided by these cells for neurons, perhaps contributing to neurodegeneration.<\/jats:p>","DOI":"10.1523\/jneurosci.0567-10.2010","type":"journal-article","created":{"date-parts":[[2010,5,5]],"date-time":"2010-05-05T19:47:39Z","timestamp":1273088859000},"page":"6236-6246","source":"Crossref","is-referenced-by-count":139,"title":["Neurodegeneration in a Transgenic Mouse Model of Multiple System Atrophy Is Associated with Altered Expression of Oligodendroglial-Derived Neurotrophic 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