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Degeneration of axons in spinal white matter in G93A mSOD1 mouse characterized by NFL and alpha internexin immunoreactivity


King, AE and Blizzard, CA and Southam, KA and Vickers, JC and Dickson, TC, Degeneration of axons in spinal white matter in G93A mSOD1 mouse characterized by NFL and alpha internexin immunoreactivity, Brain Research, 1465 pp. 90-100. ISSN 0006-8993 (2012) [Refereed Article]

Copyright Statement

Copyright 2012 Elsevier.

DOI: doi:10.1016/j.brainres.2012.05.018


Axonal degeneration is a prominent feature of amyotrophic lateral sclerosis (ALS) both in lower motor nerves as well as descending white matter axons in the spinal cord of human patients. Although the pathology of lower motor axonal degeneration has been described in both human ALS and related transgenic animal models, few studies have examined the pathological features of descending axon degeneration, particularly in mouse models of ALS. We have examined the degeneration of white matter tracts in the G93A mutant superoxide dismutase-1 (mSOD1+) mouse spinal cord white matter from 12 weeks of age to end-stage disease. In a G93A mSOD1 mouse model where green fluorescent protein was expressed in neurons (mSOD1+/GFP+), degeneration of white matter tracts was present from the ventral to dorsolateral funiculi. This pattern of axonal pathology occurred from 16 weeks of age. However, the dorsal funiculus, the site of the major corticospinal tract in mice, showed relatively less degeneration. Immunohistochemical analysis demonstrated that the neurofilament light chain (NFL) and neuronal intermediate filament protein alpha-internexin accumulated in axon swellings in the spinal white matter. Increased levels of alpha-internexin protein, in mSOD1+ mouse spinal cord tissue, were demonstrated by Western blotting. In contrast, degenerating axons did not show obvious accumulations of neurofilament medium and heavy chain proteins (NFM and NFH). These data suggest that white matter degeneration in this mouse model of ALS is widespread and involves a specific molecular signature, particularly the accumulation of NFL and alpha-internexin proteins.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:King, AE (Professor Anna King)
UTAS Author:Blizzard, CA (Dr Catherine Blizzard)
UTAS Author:Southam, KA (Dr Katherine Southam)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:Dickson, TC (Professor Tracey Dickson)
ID Code:81072
Year Published:2012
Web of Science® Times Cited:13
Deposited By:Medicine
Deposited On:2012-11-22
Last Modified:2017-11-06

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