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Title page for ETD etd-01142010-160908


Type of Document Dissertation
Author Helmcke, Kirsten Jeanne
Author's Email Address kirsten.j.helmcke@gmail.com
URN etd-01142010-160908
Title Caenorhabditis elegans as a model to study molecular mechanisms of methylmercury toxicity
Degree PhD
Department Pharmacology
Advisory Committee
Advisor Name Title
BethAnn McLaughlin Committee Chair
Ariel Deutch Committee Member
David Miller Committee Member
Eugenia Gurevich Committee Member
Michael Aschner Committee Member
Keywords
  • Caenorhabditis elegans
  • methylmercury
  • toxicity
Date of Defense 2010-01-07
Availability unrestricted
Abstract
Methylmercury (MeHg), a known neurotoxicant, is found in seafood, leading to regular exposure of humans to this compound. Many of the molecular targets and detoxifying components of MeHg toxicity, including glutathione (GSH), metallothioneins (MTs), and heat shock proteins (HSPs) have been identified; however, the molecular mechanisms of MeHg neurotoxicity are largely unknown. We used the model organism, Caenorhabditis elegans, to elucidate some of these mechanisms. We found that, although MeHg accumulated within C. elegans and caused a delay in development and a decrease in pharyngeal pumping rate, many endpoints, including life span, brood size, thrashing rate, and, most surprisingly, nervous system morphology, were unaffected. This finding led to the hypothesis that C. elegans has unique mechanisms for protecting its nervous system from MeHg neurotoxicity. We examined the involvement of GSH, MTs, and HSPs in MeHg toxicity in C. elegans and found that GSH levels were altered upon MeHg exposure, a glutathione s-transferase was highly upregulated upon exposure, and that the lack of MTs in MT knockout animals resulted in increased sensitivity to this toxicant. We also demonstrated that MeHg can induce hormesis in C. elegans, likely at least partially due to the involvement of GSTs in MeHg toxicity. As a result of our findings, we began to elucidate some of the molecular mechanisms of MeHg neuroprotection in the C. elegans model system. Our findings are highly valuable to the field of human health due to the regular exposure of humans to MeHg.
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