Date of Award

January 2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

First Advisor

Jonathan D. Geiger

Second Advisor

Joyce E. Ohm

Abstract

Natural toxins and artificial toxicants are abundant throughout our environment and may play an integral role in remodeling our epigenome and in the development of neural diseases. Exposure to heavy metals and organic pollutants, such as DDT and its derivatives, have been linked to neural disease. Additionally, there are links between direct exposure, in both adults and children, to short-lived pesticides and neural diseases. While the link has been established, understanding the root cause has yet to be elucidated. One increasingly relevant field offering promise in achieving this goal is epigenetics. Epigenetic remodeling is one potential mechanism by which environmental exposures may lead to human disease. Epigenetic remodeling events have been increasingly implicated in the underpinnings of a variety of brain disorders including neurodegenerative disorders and cancer. We hypothesize that environmental exposures and associated epigenetic remodeling events may occur early in life during the critical development stages and play a role in long term development of many neural diseases. We examine the current status of the field and highlight areas in need of attention and propose a model toxicant for understanding the effects of early epigenetic remodeling events and the impact of disease by examining the ability of the environmental toxicant Paraquat to remodel the epigenome both in vitro and in vivo, and investigate whether exposures in early development may be linked to disease.

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