Home WakeSpace Scholarship › Electronic Theses and Dissertations

MACROPHAGE RESPONSE TO INITIAL MUSCLE DENERVATION IN THE SOD1-G93A MOUSE MODEL OF AMYTROPHIC LATERAL SCLEROSIS.

Electronic Theses and Dissertations

Item Files

Item Details

abstract
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset motor neuron (MN) disease characterized by dysfunction, degeneration and death of upper and lower MNs. Loss of the connections of MN to muscle at the neuromuscular junction (NMJ) underlies the characteristic muscle weakness seen in ALS. NMJs from fast-fatigable (FF) MNs preferentially denervate early in the disease process compared to fast-fatigue resistant (FR) and slow (S) NMJs. In the SOD1G93A mouse model of ALS, initial NMJ denervation occurs in the TA muscle (FF and FR fibers) between postnatal day (P)14 and P30, while little denervation occurs in soleus muscle (S and FR fibers) even late in disease. It is plausible that early alterations in the neuronal microenvironment could create MN vulnerability which may ultimately affect survival of the MN. Indeed while motor neurons are the primary targets in ALS, non-neuronal cells such as glial cells and immune/inflammatory cells are also known contributors to pathology. While the response of non-neuronal cells in the CNS has been well-characterized in ALS, little is known about the inflammatory response in skeletal muscle and how this response may influence NMJ denervation and MN survival. Using immunofluorescence, we found significant increases in macrophage immunoreactivity in TA muscles beginning at P60. Significant increases were not seen in soleus until endstage. Results suggest an early, progressive and rather robust macrophage response around NMJs and peripheral nerves in SOD1G93A mouse skeletal muscles.
subject
ALS
Inflammation
Macrophage
Neurodegeneration
contributor
Gillespie, Rachel (author)
Milligan, Carol (committee chair)
Hawkins, Gregory (committee member)
date
2017-08-22T08:35:22Z (accessioned)
2019-08-21T08:30:11Z (available)
2017 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2019-08-21 (terms)
identifier
http://hdl.handle.net/10339/86338 (uri)
language
en (iso)
publisher
Wake Forest University
title
MACROPHAGE RESPONSE TO INITIAL MUSCLE DENERVATION IN THE SOD1-G93A MOUSE MODEL OF AMYTROPHIC LATERAL SCLEROSIS.
type
Thesis

Usage Statistics