Year of Award

2014

Document Type

Thesis

Degree Type

Master of Science (MS)

Degree Name

Toxicology

Department or School/College

Department of Biomedical and Pharmaceutical Sciences

Committee Chair

Fernando Cardozo-Pelaez

Commitee Members

Richard Bridges, Andrij Holian, Sarah Certel

Keywords

Environmental Toxic Model, Parkinson's Disease, Fruit Fly

Publisher

University of Montana

Subject Categories

Molecular and Cellular Neuroscience | Other Pharmacology, Toxicology and Environmental Health | Toxicology

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with no known specific cause; although genetic risk factors and/or environmental exposure are thought to be involved. The etiology of PD is currently unknown, although the combination of non-genetic components such as environmental exposures, the accumulation of exposure, and gene-environment interactions are thought to play a major role. However, despite this knowledge it is important to develop better models that parallel PD pathophysiology to further understand the mechanisms underlying dopaminergic neuron (DaN) damage. The use of mammalian models to study the degenerative processes in PD has been the most common approach. However, Drosophila melanogaster use has proven to be important to identify the physiological role of PD associated genes, and to identify pathological mechanisms of environmental toxins associated with sporadic PD. The synthetic drug MPTP (1-methyl- 4-phenyl-1,2,3,4-tetrahydropyridine) has been extensively used to generate animal models of PD. MPTP is the most used toxin model with highly reproducible effects in mice and non-human primates, and its use is a requirement for the development of new therapeutic approaches. However, MPTP neurotoxicity has not been reported in D. melanogaster. Results from the studies presented in this thesis show that Drosophila exposure to MPTP may be a useful model of PD, as evidenced by: loss of brain DA, reduction in tyrosine-hydroxylase positive neurons and inhibition of mitochondrial complex I. Thus, taken together this recapitulates the mammalian model

 

© Copyright 2014 Jennene Lyda