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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2013

Open Access 01-12-2013 | Research

Dysregulation of the complement cascade in the hSOD1G93Atransgenic mouse model of amyotrophic lateral sclerosis

Authors: John D Lee, Nur A Kamaruzaman, Jenny NT Fung, Stephen M Taylor, Bradley J Turner, Julie D Atkin, Trent M Woodruff, Peter G Noakes

Published in: Journal of Neuroinflammation | Issue 1/2013

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Abstract

Background

Components of the innate immune complement system have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS); however, a comprehensive examination of complement expression in this disease has not been performed. This study therefore aimed to determine the expression of complement components (C1qB, C4, factor B, C3/C3b, C5 and CD88) and regulators (CD55 and CD59a) in the lumbar spinal cord of hSOD1G93A mice during defined disease stages.

Methods

hSOD1G93A and wild-type mice were examined at four different ages of disease progression. mRNA and protein expression of complement components and regulators were examined using quantitative PCR, western blotting and ELISA. Localisation of complement components within lumbar spinal cord was investigated using immunohistochemistry. Statistical differences between hSOD1G93A and wild-type mice were analysed using a two-tailed t-test at each stage of disease progression.

Results

We found several early complement factors increased as disease progressed, whilst complement regulators decreased; suggesting overall increased complement activation through the classical or alternative pathways in hSOD1G93A mice. CD88 was also increased during disease progression, with immunolocalisation demonstrating expression on motor neurons and increasing expression on microglia surrounding the regions of motor neuron death.

Conclusions

These results indicate that local complement activation and increased expression of CD88 may contribute to motor neuron death and ALS pathology in the hSOD1G93A mouse. Hence, reducing complement-induced inflammation could be an important therapeutic strategy to treat ALS.
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Metadata
Title
Dysregulation of the complement cascade in the hSOD1G93Atransgenic mouse model of amyotrophic lateral sclerosis
Authors
John D Lee
Nur A Kamaruzaman
Jenny NT Fung
Stephen M Taylor
Bradley J Turner
Julie D Atkin
Trent M Woodruff
Peter G Noakes
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-10-119

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