|
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 text | SMody.pdf |
| |