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Open Access Highly Accessed Research article

Comparative analysis of the time-dependent functional and molecular changes in spinal cord degeneration induced by the G93A SOD1 gene mutation and by mechanical compression

Andrea Malaspina*, Natasa Jokic, Wenlong L Huang and John V Priestley

Author Affiliations

Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, Whitechapel, London E1 2AT, UK

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BMC Genomics 2008, 9:500  doi:10.1186/1471-2164-9-500

Published: 23 October 2008

Abstract

Background

Mutations of the superoxide dismutase 1 (SOD1) gene are linked to amyotrophic lateral sclerosis (ALS), an invariably fatal neurological condition involving cortico-spinal degeneration. Mechanical injury can also determine spinal cord degeneration and act as a risk factor for the development of ALS.

Results

We have performed a comparative ontological analysis of the gene expression profiles of thoracic cord samples from rats carrying the G93A SOD1 gene mutation and from wild-type littermates subjected to mechanical compression of the spinal cord. Common molecular responses and gene expression changes unique to each experimental paradigm were evaluated against the functional development of each animal model. Gene Ontology categories crucial to protein folding, extracellular matrix and axonal formation underwent early activation in both experimental paradigms, but decreased significantly in the spinal cord from animals recovering from injury after 7 days and from the G93A SOD1 mutant rats at end-stage disease. Functional improvement after compression coincided with a massive up-regulation of growth-promoting gene categories including factors involved in angiogenesis and transcription, overcoming the more transitory surge of pro-apoptotic components and cell-cycle genes. The cord from G93A SOD1 mutants showed persistent over-expression of apoptotic and stress molecules with fewer neurorestorative signals, while functional deterioration was ongoing.

Conclusion

this study illustrates how cytoskeletal protein metabolism is central to trauma and genetically-induced spinal cord degeneration and elucidates the main molecular events accompanying functional recovery or decline in two different animal models of spinal cord degeneration.