Date of Award

5-2010

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Dr. Charles F. Ide

Second Advisor

Dr. Rob Eversole

Third Advisor

Dr. John Spitsbergen

Access Setting

Masters Thesis-Campus Only

Abstract

Multiple System Atrophy (MSA) is a sporadic, neurodegenerative disease with varied clinical phenotypes that include Parkinsonism and cerebellar and autonomic dysfunction. Glial cytoplasmic inclusions (GCIs), aggregates of the presynaptic protein a-synuclein, appear in oligodendrocytes in MSA. In this study, the amount of a-synuclein was measured in multiple regions of the rostral pons using quantitative image analysis. Alpha-synuclein was significantly increased in the dorsal-most pontocerebellar fiber tract, in pontocerebellar fiber tracts ventral to the dorsal-most tract, in adjacent non-pontocerebellar fiber tracts (corticopontine, corticobulbar, corticospinal), and in the central tegmental tract of MSA patients compared to controls. The distribution of a-synuclein in these specific tracts is consistent with pontocerebellar involvement in MSA. In addition, the amount of a-synuclein in the four analyzed regions varied amongst MSA patients, and may be associated with the severity of specific symptoms in different patients. Increased amounts of a-synuclein in the dorsal-most pontocerebellar fiber tract correlated with changes in global gene expression, most notably changes in genes associated with oligodendrocyte and mitochondrial functions, the inflammatory/stress response, and protein degradation processes.

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