Document Type

Thesis

Date of Degree

Fall 2017

Access Restrictions

Access restricted until 01/31/2019

Degree Name

MS (Master of Science)

Degree In

Biology

First Advisor

Chun-Fang Wu

First Committee Member

Daniel Eberl

Second Committee Member

Thoshihiro Kitamoto

Abstract

Oxidative stress has a degenerative effect on neuronal health. Mutations in the copper zinc superoxide dismutase (SOD1), an important antioxidant, have been found in patients suffering from amyotrophic lateral sclerosis (ALS). Classical EMS induced mutations to SOD1 in Drosophila show similar loss of motor coordination and shortened lifespan seen in humans. A study of newly created human ALS point mutants along with the classic alleles show similar phenotypes in their neurodegeneration. I examined markers of oxidative stress, neuronal health and behavioral phenotypes throughout the lifecycle of aging flies. Larvae were largely found to be unaffected by mutations in SOD1, with no measured increase in ROS level over wild type (WT) flies. Mutant pupae were found to have two major defects in their circadian eclosion rhythm and their fundamental ability to eclose from the pupal casing. Adults showed the classic reduced lifespan and motor abilities. To further examine the health on non-glutamatergic synapses electroretinograms (ERGs) were recorded at different levels of survivorship indicated by Kaplan-Meier Survival curves. These ERGs show that the histaminergic synapses they record have greater degeneration in aging SOD1 mutants than in WT flies. This is true for their chronological age as well as their biological age. There was coinciding disruption of the photo transduction pathway of the photoreceptors that coincided with degeneration at the synapse. This demonstrates the separate degenerative effect of high levels of oxidative stress impart separate for the normal aging process.

Keywords

ALS, Drosophila, ERG, Neurodegeneration, Neurogenetics, SOD

Pages

ix, 41 pages

Bibliography

Includes bibliographical references (pages 37-41).

Copyright

Copyright © 2017 Scott Andrew Woods

Available for download on Thursday, January 31, 2019

Included in

Biology Commons

Share

COinS