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Neuron-glia interactions underlie ALS-like axonal cytoskeletal pathology


King, AE and Dickson, TC and Blizzard, CA and Woodhouse, A and Foster, SS and Chung, RS and Vickers, JC, Neuron-glia interactions underlie ALS-like axonal cytoskeletal pathology, Neurobiology of Aging: Experimental and Clinical Research, 32, (3) pp. 459-469. ISSN 0197-4580 (2011) [Refereed Article]

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DOI: doi:10.1016/j.neurobiolaging.2009.04.004


Amyotrophic lateral sclerosis (ALS) is a devastating disorder involving loss of movement due to degeneration of motor neurons. Studies suggest that in ALS axonal dysfunction precedes the death of motor neurons. Pathologically, ALS is characterized by neurofilamentous swellings (spheroids) within the axons of motor neurons. However, the causes of this axonopathy and possible resulting axonal dysfunction are not known. Using a novel model of cultured mouse motor neurons, we have determined that these neurons are susceptible to proximal axonopathy, which is related to the glial environment. This axonopathy showed remarkable similarity, both morphologically and neurochemically, to spheroids that develop over months in SOD1G93A transgenic mice. Focal ubiquitination, as well as perturbations of neurofilaments and microtubules, occurred in the axonal spheroid-like swellings in vitro, and visualization of mitochondrial dynamics demonstrated that axonopathy resulted in impaired axonal transport. These data provide strong evidence for the involvement of non-neuronal cells in axonal dysfunction in ALS. This cell culture model may be of benefit for the development of therapeutic interventions directed at axonal preservation.

Item Details

Item Type:Refereed Article
Keywords:ALS; Neurofilament; Motor neuron; Axon; Glia
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:King, AE (Professor Anna King)
UTAS Author:Dickson, TC (Professor Tracey Dickson)
UTAS Author:Blizzard, CA (Dr Catherine Blizzard)
UTAS Author:Woodhouse, A (Dr Adele Woodhouse)
UTAS Author:Foster, SS (Miss Sandessa Foster)
UTAS Author:Chung, RS (Associate Professor Roger Chung)
UTAS Author:Vickers, JC (Professor James Vickers)
ID Code:60708
Year Published:2011
Web of Science® Times Cited:24
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-02-16
Last Modified:2017-11-06

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