Abstract

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence of glutamate transport dysfunction and oxidative stress following radiation. To achieve this objective, we utilized the NTera2/Dl cell line which was induced to differentiate into neurons and astrocytes. Neuron and astrocyte cultures were then exposed to ionizing radiation and changes in glutamate transport and antioxidant levels were measured to ascertain the temporal relationship between glutamate dysfunction and cellular antioxidant capacity. We examined alterations in glutamate transport dysfunction as an underlying mechanism of radiation-induced neurotoxicity. In particular, we examined specific cellular and molecular factors of glutamate transport dysfunction in order to elucidate a specific mechanism of radiation-induced neuronal damage. Thus, we were able to observe acute functional changes at a cellular and molecular level, thereby allowing us to ascertain the probability that radiation exposure will result in long-term neurodegenerative effects.

LLU Discipline

Physiology

Department

Physiology

School

Graduate Studies

First Advisor

Lora M. Green

Second Advisor

Danilyn M. Angeles

Third Advisor

Gregory A. Nelson

Fourth Advisor

Marcelo E. Vazquez

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2008

Date (Title Page)

3-2008

Language

English

Library of Congress/MESH Subject Headings

Central Nervous System -- physiology -- dissertations; Amino Acid Transport System X-AG -- metabolism; Atrocytes -- metabolism -- radiation effects; Biological Transport -- radiation effects; . Cell Line, Tumor; Dose-Response Relationship, Radiation; Gamma Rays -- adverse effects; Glutamic Acid -- metabolism; Neurons -- metabolism -- radiation effects

Type

Dissertation

Page Count

xv; 127

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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