Effects of mitochondrial dynamics genes, fzo-1 and drp-1, on dopaminergic neurodegeneration induced by environmental exposure in Caenorhabditis elegans, as a model of Parkinson’s disease

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2015-05-30

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Abstract

Parkinson’s disease (PD) is caused by degeneration of the dopaminergic neurons; environmental toxicants are hypothesized to play a role in PD etiology. Environmental toxicants can cause mitochondrial dysfunction through mitochondrial DNA (mtDNA) damage and production of reactive oxygen species. Serial ultraviolet C (UVC) radiation causes an accumulation of mtDNA damage and 6-hydroxydopamine (6-OHDA) causes loss of dopaminergic neurons. Mitochondrial dynamics, or fusion and fission of the mitochondria, are important processes in mitigating mitochondrial dysfunction. The fzo-1 and drp-1 genes in Caenorhabditis elegans are orthologs for human Mfn1/2 and Drp1 and are involved in mitochondrial fusion and fission, respectively. I tested the hypothesis that deletion mutant strains for these two genes would show increased neurodegeneration after environmental damage, relative to the wild-type control strain, due to the lack of normal mitochondrial dynamics. Unexpectedly, both the fzo-1 and drp-1 were protected against 6-OHDA-induced neurodegeneration relative to wild-type. The fzo-1 knockout underwent complete larval arrest after UVC exposure, suggesting that mitochondrial fusion is necessary for recovery after mtDNA damage. The drp-1 mutant showed slightly more neurodegeneration than wild-type after UVC exposure at the 10 J/m2 dose, but not the 7.5 J/m2 dose. These results highlight the significance of mitochondrial dynamics and gene-environment interactions in dopaminergic neurodegeneration and PD etiology.

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Honors Thesis submitted for graduation with Distinction in Biology and Environmental Sciences in Trinity College of Duke University

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Hall, Samantha (2015). Effects of mitochondrial dynamics genes, fzo-1 and drp-1, on dopaminergic neurodegeneration induced by environmental exposure in Caenorhabditis elegans, as a model of Parkinson’s disease. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/10199.


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