Dopamine homeostasis and environmental risk factors in Parkinson's Disease model

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dc.contributor Johnson, Margaret
dc.contributor Smith-Somerville, Harriett
dc.contributor Churchill, Perry F.
dc.contributor Vincent, John B.
dc.contributor.advisor O'Donnell, Janis M. Wright, O'Neil Antonio 2017-03-01T14:43:45Z 2017-03-01T14:43:45Z 2011
dc.identifier.other u0015_0000001_0000652
dc.identifier.other Wright_alatus_0004D_10853
dc.description Electronic Thesis or Dissertation
dc.description.abstract The neurotransmitter dopamine (DA) is an important factor in the regulation of many biological processes, from pleasure and addiction to balance and locomotion. Therefore, understanding and defining the mechanisms and factors that are required for proper DA homeostasis is an integral component in managing and elucidating the causes of DA related diseases. Among these diseases, Parkinson's disease (PD) is the most notable and remains one of the most researched yet puzzling motor system associated neurological disorders. PD is characterized by a preferential loss of DA neurons in the substantia nigra. Though the cause and exact mechanism of this disease remains undefined, numerous environmental factors such as metals and pesticides have been associated with the etiology of the disease process. In the following studies, the genetic components of DA homeostasis and environmental risk factors in a Drosophila model of PD are investigated. The implication of metals as a component in the pathology of PD is examined in relationship to zinc toxicity. Catecholamines's up (Catsup), which plays a crucial role in regulating DA homeostasis and is proposed to be a member of the mammalian KE4 ZIP transporter family, demonstrates zinc sensitivity, with the proposed underlying factors being a dysregulation of DA synthesis and DA transport. The findings of this report demonstrate that loss of dopamine transporter (DAT) function, results in a more robust sensitivity to zinc than that seen in Catsup mutants. In addition exogenous DA increases sensitivity of wild type flies to zinc, similar to that which is seen Catsup mutants. Interestingly, LiCl ameliorates the toxic effects of zinc. The results also demonstrate a functional relationship between paraquat toxicity and DAT, which affects DA transport. To determine the consequences of early exposure to paraquat on lifespan and mobility, the effect of a one time exposure to young adult flies was observed. The results of this experiment show that a brief exposure to paraquat illicts long term detrimental affects on survival as well as parkinsonian type phenotypes.
dc.format.extent 143 p.
dc.format.medium electronic
dc.format.mimetype application/pdf
dc.language English
dc.language.iso en_US
dc.publisher University of Alabama Libraries
dc.relation.ispartof The University of Alabama Electronic Theses and Dissertations
dc.relation.ispartof The University of Alabama Libraries Digital Collections
dc.relation.hasversion born digital
dc.rights All rights reserved by the author unless otherwise indicated.
dc.subject.other Biology
dc.title Dopamine homeostasis and environmental risk factors in Parkinson's Disease model
dc.type thesis
dc.type text University of Alabama. Dept. of Biological Sciences Biological Sciences The University of Alabama doctoral Ph.D.

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