Drew University Library : University Archives : Theses and Dissertations
    
author Shivani Mody
title The Search for Reliable Behavioral Assays to Model Parkinson's Disease in the Nematode Caenorhabditis elegans
abstract Parkinson's disease is a nervous system disorder associated with abnormal damage to dopamine neurons that play a role in reward and movement. This disease is localized to the substantia nigra region of the basal ganglia and the ventral tegmental area, with projections to the striatum (caudate and putamen). This disease is the second most common neurodegenerative disorder, after Alzheimer's disease, with an increased predisposition combining both environment and genetics. Apart from long-term pesticide and toxin exposure, mutations in leucine-rich-repeat kinase 2 (LRRK2) and α-synuclein proteins are shown to greatly influence the onset of Parkinson's. Animal models have been intensively used for the study of Parkinson's disease including rodents, non-human primates and the nematode worms, Caenorhabditis elegans. This research involves studying Parkinson's behaviors in Caenorhabditis elegans mutants because they are good models with a well-defined dopamine system, which is relevant to the mechanism of Parkinson's. In this study, we experimented with and modified multiple behavioral assays, including the swim-to-crawl assay, the movement-over-alternate-terrain (MOAT) assay, the ethanol avoidance assay, and the swimming-induced-paralysis (SWIP) assay to track and model behaviors of C. elegans mutants. We hypothesized that C. elegans worms expressing a mutant form of human leucine-rich repeat kinase 2 (LRRK2), would display a loss of dopamine neurons over time, compared to the wild-type worms and this hypothesis was tested using the ethanol avoidance assay, as previously established in literature. Based on the results, we concluded that the SWIP and MOAT assays were not well suited as an assay to model Parkinson's disease. The results we obtained from the MOAT assay were conclusive, yet not useful since we learned that C. elegans do not spontaneously transition from swimming to crawling. The SWIP assay was found to be unsuitable to examine the age-related loss of dopamine neurons because older wildtype worms lose the SWIP phenotype. In the future, we plan to focus on testing older age LRRK2 worms in the ethanol avoidance assay and reproducing the literature results for the basal-slowing response assay, as these are good models for studying Parkinson's. Potential treatments for Parkinson's have been focused on developing LRRK2 kinase inhibitors, that directly inhibit LRRK2 kinase and lead to a decreased loss of dopamine neurons, increasing neuroprotection. We plan to use our worm model of Parkinson's to identify new LRRK2 inhibitor compounds.
school The College of Liberal Arts, Drew University
degree B.S. (2021)
advisor Marvin Bayne
committee Minjoon Kouh
Adam Cassano
full textSMody.pdf