The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Shafie, I. N.F., McLaughlin, M., Burchmore, R., Lim, M. A. A., Montague, P., Johnston, P. E.J., Penderis, J. and Anderson, T. J. (2014) The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog. Cell Stress and Chaperones, 19(3), pp. 311-320. (doi:10.1007/s12192-013-0457-4)

[img]
Preview
Text
85129.pdf - Accepted Version

663kB

Publisher's URL: http://dx.doi.org/10.1007/s12192-013-0457-4

Abstract

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD.

Item Type:Articles
Additional Information:The final publication is available at link.springer.com
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Penderis, Professor Jacques and McLaughlin, Dr Mark and Shafie, Mrs Intan and Burchmore, Dr Richard and Montague, Dr Paul and Anderson, Professor Thomas and Johnston, Dr Pamela
Authors: Shafie, I. N.F., McLaughlin, M., Burchmore, R., Lim, M. A. A., Montague, P., Johnston, P. E.J., Penderis, J., and Anderson, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Cell Stress and Chaperones
Publisher:Springer Netherlands
ISSN:1355-8145
ISSN (Online):1466-1268
Copyright Holders:Copyright © 2013 Cell Stress Society International
First Published:First published in Cell Stress and Chaperones 19(3):311-320
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record