Date of Award


Degree Name

Master of Science


Biological Sciences

First Advisor

Dr. Charles F. Ide

Second Advisor

Dr. John M. Spitsbergen

Third Advisor

Dr. Cindy Linn


Alpha-synuclein, immune, mitochondria, glia, Multiple System Atrophy (MSA)

Access Setting

Masters Thesis-Open Access


Multiple System Atrophy (MSA) is a neurodegenerative disease characterized by the accumulation of misfolded α-synuclein (α-Syn) in oligodendrocytes of the central nervous system (CNS). A previous study in our lab used Affymetrix DNA microarray analysis to show the downregulation of various mitochondrial related genes, as well as the upregulation of genes involved in inflammatory/immune responses in MSA brain tissue. Therefore, it is hypothesized that an increased presence of immune proteins exists in the MSA brain accompanied by glial cell pathology including decreases in cell metabolism and cell viability. This study uses immunohistochemistry (IHC) to show the increased presence of CD68 and CD33, two microglia/macrophage associated proteins, and a greater number of CD8α positive lymphocytes in the pontocerebellar tracts of MSA pons. This suggests an immune response mediated by microglia and/or macrophage cells, as well as cytotoxic T cells in an area of the brain plagued by α-Syn. In addition to increased immune activity, glial cells are directly affected in MSA. This study uses a cell culture model of MSA comprised of C6 glioma cells treated with exogenous α-Syn. Cells exhibited less dehydrogenase activity accompanied by decreases in total cell number without significant loss of cell viability, decreased mitochondrial membrane potential was also detected. These data suggest decreases in cell metabolism via mitochondrial dysfunction and cell loss, potentially from reduced proliferation, contribute to the pathogenesis of MSA.