Document Type

Honors Thesis

Publication Date

5-2014

Abstract

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. Given its prevalence, researching PD is important to world health. The well known motor symptoms of PD are often accompanied by non-motor symptoms (NMS) including visuo-spatial learning and memory deficits. However, the mechanism whereby these NMS occur is unknown. PD is also characterized by the presence of protein aggregates termed Lewy Bodies (LBs). The mechanism whereby LBs form is unclear, although the fibrillization and aggregation of α-synuclein seem to be critical contributing factors.

This thesis reports development of an animal model of PD to study NMS using 6-Hydroxydopamine (6-OHDA) to produce partial bilateral lesions to the striata of mice. These lesions significantly reduced the tyrosine hydroxylase immunoreactivity in the striatum and hippocampus, mimicking the loss observed in PD patients. A deficit in visuo-spatial learning and memory in 6-OHDA treated mice was documented using the Barnes maze and Spatial Object Recognition test. Therefore, this model is expected to be useful for future study of the cause of these NMS.

An analysis of mechanisms reported to underlie LB formation revealed the potential importance of the protease calpain and the peptidyl-prolyl isomerase PIN1 in α-synuclein fibrillization. Data from the literature demonstrated that calpain cleaves α-synuclein, promoting its aggregation, and PIN1 potentially regulates calpain activity. Preliminary data reveal that calpain-2 cleaves PIN1 in vitro. The relationship between cal pain and PIN1 should be examined further in regards to PD.

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