Investigating the Effects of Atlastin-1 on Spastin and REEP1 Using Primary Cultured Neurons from Mice with Motor Neuron Disease
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Authors
Edsall, Taryn N.
Issue Date
2013
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Impairment of axonal transport is a common cause of motor neuron degeneration
and is associated with many neurological disorders including Alzheimer's disease,
Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), and
hereditary spastic paraplegia (HSP). HSP affects approximately 1.27-9.6 per 100,000
people, and pathologically leads to length-dependent retrograde degeneration of
corticospinal neurons. Over .half of all cases of autosomal dominant HSP are caused by
mutations in spastin, atlastin-1, or REEP1. These proteins co-localize and bind together
in the endoplasmic reticulum (ER) via intramembrane hydrophobic hairpin domains and
are directly involved in the coordination of ER shaping and microtubule dynamics in
corticospinal neurons. To understand the possible effects of eliminating the protein
atlastin-1 in mouse models, this study used primary cortical neuron cultures from adult
knockout atlastin mice. Immunocytochemistry was performed on these cultured neurons,
staining for spastin, atlastin-1, and REEP 1 to determine how the quantity of atlastin
affects the location and quantity of spastin and REEP 1, as well as axon length in neurons.
While it was confirmed that atlastin levels were significantly less in heterozygous
cultures, overall protein levels of spastin and REEP 1 decreased in heterozygous cultures,
however they were not statistically significant. Future experimentation with atlastin
knockout mice will.allow for an increased understanding of the relationships between
axonal transport and motor neuron degeneration, which is imperative for the development
of molecular-targeted therapies and biomarkers in HSP, as well as other motor neuron
diseases.
Description
v, 32 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.