The Formation of Cytoplasmic Rods in Spinal Cord Neurons: A Study of the Effects of Oxidative Stress
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Authors
Stehman, Christine R.
Issue Date
1999
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
A prominent hallmark of amyotrophic lateral sclerosis (ALS) is the presence of
proteinaceous cytoplasmic inclusion bodies that contain the cytoskeletal protein actin in
neurons. We and others have shown that energy depletion and oxidative stress can
induce cytoplasmic rods in cortical and hippocampal neurons. These rods, which contain
actin and at least one member of the actin-depolymerizing factor (ADF)/cofilin family of
proteins, are thought to be precursors to inclusion bodies. Our goal was to determine if
similar conditions would induce the formation of rods in spinal cord neurons. We
previously observed the generation of spontaneous rods in spinal cord neurons. To
combat this problem, we added antioxidants to growth medium and found that they
decreased spontaneous rod formation. In addition, ATP-depletion and peroxide exposure
induced rods in spinal cord neurons grown in medium containing antioxidants. The rods
induced by ATP-depletion were reversible. In contrast, those induced by peroxide
exposure were not. Furthermore, a rapid dephosphorylation (activation) of ADF and
cofilin preceded rod formation. Finally, our studies suggest that a minimum level of
ADF is critical for rod formation because Swiss 3T3 fibroblasts do not form rods and
contain one-third the ADF of cortical neurons and one-ninth the ADF of spinal cord
neurons. We propose that oxidative stress and energy depletion promote the formation of
ADF /cofilin-actin rods, which may contribute to the neurodegeneration associated with
ALS.
With honors.
With honors.
Description
vi, 48 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.