Blockade of C5a receptors reduces astroglial inflammation in a rat SOD1G93A model of amyotrophic lateral sclerosis

Woodruff, Trent, Denny, Kerina, Crane, James, Atkin, Julie, Taylor, Steve and Noakes, Peter (2008). Blockade of C5a receptors reduces astroglial inflammation in a rat SOD1G93A model of amyotrophic lateral sclerosis. In: Robert Rieben, Molecular Immunology.. ICW Basel, XXII International Complement Workshop, Basel, Switzerland, (4163-4182). 28 September-02 October 2008.


Author Woodruff, Trent
Denny, Kerina
Crane, James
Atkin, Julie
Taylor, Steve
Noakes, Peter
Title of paper Blockade of C5a receptors reduces astroglial inflammation in a rat SOD1G93A model of amyotrophic lateral sclerosis
Formatted title Blockade of C5a receptors reduces astroglial inflammation in a rat SOD1G93A model of amyotrophic lateral sclerosis
Conference Paper Type Published Abstract
Conference name ICW Basel, XXII International Complement Workshop
DOI 10.1016/j.molimm.2008.08.202
Conference location Basel, Switzerland
Conference dates 28 September-02 October 2008
Proceedings title Molecular Immunology.  (ERA 2012 Listed)    (ERA 2010 Rank B)   Check publisher's open access policy
Journal name Molecular Immunology  (ERA 2012 Listed)    (ERA 2010 Rank B)   Check publisher's open access policy
Editor Robert Rieben
Publication date 2008
Volume number 45
Issue number 16
ISSN 0161-5890
Start page 4163
End page 4182
Total pages 142
Language eng
Abstract/Summary Amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease, is a fatal neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons leading to muscle paralysis and eventual death. It remains a disease that is largely untouched by current therapeutics. Transgenic animals harboring mutant human SOD1G93A enzyme found in familial cases of ALS, develop similar pathology to the human condition, and are thus used as an animal model to test out new therapeutics. Several years ago, our laboratory developed a series of potent drugs (C5a receptor antagonists) which block the action of the complement factor C5a. We have previously demonstrated that SOD1 transgenic rats treated with one of these drugs (hydrocinnamate-[OPdChaWR]; PMX205), was able to improve survival (127 ± 4 days vs. 144 ± 8 days) and reduce end-stage motor deficits. The present study aimed to examine these effects further using immunohistochemical techniques. Lumbar spinal cord tissue from wild-type, untreated SOD1, and PMX205-treated SOD1 transgenic rats were immuno-stained with antibodies for motor neurons, astrocytes, microglia and C5a receptors. We observed a significant upregulation of both astrocytes and microglia in SOD1G93A rats (34-fold and 21-fold increase, respectively), corresponding with motor neuron loss in these same regions. Interestingly, we found C5a receptors to be strongly expressed on these proliferating astrocytes, but not on microglia. C5a receptors were also found on motor neurons in both wild-type and SOD1G93A rats. PMX205 treatment was found to significantly reduce the degree of astrocyte proliferation in end-stage SOD1G93A rats, but treatment had no effect on microglial proliferation. This study indicates that PMX205 may exert its protective effect in the SOD1G93A rat by reducing astroglial inflammation. Inhibitors of C5a may therefore serve as potential novel therapeutics to treat this disease. Copyright © 2009 Elsevier Ltd. All rights reserved
Subjects 1107 Immunology
Keyword Amyotrophic lateral sclerosis (ALS)
Motor Neuron Disease
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Proceedings of XXII International Complement Workshop in Basel, Switzerland, September 2008.

Document type: Conference Paper
Sub-type: Published Abstract
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Google Scholar Search Google Scholar
Access Statistics: 90 Abstract Views  -  Detailed Statistics
Created: Mon, 14 Sep 2009, 09:27:23 EST by Therese Egan on behalf of Faculty of Science