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Multiple system atrophy (MSA) is a neurodegenerative disorder. Previous studies by Holmberg (2004) found excess amounts of alpha synuclein (SNCA) diffused in the tracts of MSA patients. This finding lead to the hypothesis that neurodegeneration in MSA is caused by death of oligodendroglia via cytoplasmic inclusions containing misfolded SNCA (Wenning et. al., 2004). In normal cerebellar folia, SNCA is produced by cerebellar granule cells situated near the fiber tracts that contain oligodendroctytes. Thus, the aim of my research was to test the idea that, in MSA, the granule cell layer exports misfolded SNCA to nearby fiber tracts that contain oligodendrocytes. The MSA granule cell layer would have less SNCA compared to the control granule cell layer, and the MSA fiber tracts would have more SNCA than control tracts. In addition, the research tested the idea that a protein, hook3, which moves other proteins to the golgi apparatus for secretion, would mimic the presence of SNCA in MSA versus control tissues. Quantitative image analysis (Image J) on cerebellar sections stained via IHC for both SNCA (AP) and hook3 (DAB) showed trends consistent with SNCA and hook3 integrated densities being reduced in the granule layer and increased in nearby fiber tracts (not significant, p=0.237, ANOVA, 1 between, 2 within; SPSS). Since the analysis was limited by material being available from only four MSA and four control patients, these results encourage further studies comparing protein differences within the granule cell layer and nearby fiber tracts in additional samples.
Peterson, Alyssa, "The Difference of Alpha Synuclein and Hook3 in Control and Multiple System Atrophy Experimental Patients" (2014). Honors Theses. 2451.