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Disruption of the Ubiquitin Proteasome System following Axonal Stretch Injury Accelerates Progression to Secondary Axotomy

Citation

Staal, JA and Dickson, TC and Chung, RS and Vickers, JC, Disruption of the Ubiquitin Proteasome System following Axonal Stretch Injury Accelerates Progression to Secondary Axotomy, Journal of Neurotrauma, 26, (5) pp. 781-788. ISSN 0897-7151 (2009) [Refereed Article]

DOI: doi:10.1089/neu.2008.0669

Abstract

The ubiquitin proteasome system (UPS) plays a vital role in the regulation of protein degradation. Ubiquitination of proteins has been implicated in the pathological cascade associated with neuronal degeneration in both neurodegenerative disease and following acquired central nervous system (CNS) injury. In the present study, we have investigated the role of the UPS following mild to moderate in vitro axonal stretch injury to mature primary cortical neurons, a model of the evolving axonal pathology characteristic of diffuse axonal injury following brain trauma. Transient axonal stretch injury in this model does not involve primary axotomy. However, delayed accumulation of ubiquitin in neuritic swellings at 48 h post-injury (PI) was present in axonal bundles, followed by approximately 60% of axonal bundles progressing to secondary axotomy at 72 h PI. This delayed accumulation of ubiquitin was temporally and spatially associated with cytoskeletal damage. Pharmacological inhibition of the UPS with both MG132 and lactacystin prior to axonal injury resulted in a significant (p < 0.05) increase in the number of axonal bundles progressing to secondary axotomy at 48 and 72 h PI. These results demonstrate that, following mild to moderate transient axonal stretch injury, UPS activity may assist structural reorganization within axons, potentially impeding secondary axotomy. Protein ubiquitination in the axon may therefore have a protective role relative to the diffuse axonal changes that follow traumatic brain injury.

Item Details

Item Type:Refereed Article
Keywords:axonal injury; axonal swellings; cytoskeleton; lactacystin; MG132; neurofilament; ubiquitin
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Staal, JA (Dr Jerome Staal)
Author:Dickson, TC (Professor Tracey Dickson)
Author:Chung, RS (Associate Professor Roger Chung)
Author:Vickers, JC (Professor James Vickers)
ID Code:60717
Year Published:2009
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-02-16
Last Modified:2010-04-16
Downloads:0

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