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Spinal Cord mRNA Profile in Patients with ALS: Comparison with Transgenic Mice Expressing the Human SOD-1 Mutant

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Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor neurons in the cerebral cortex, brain stem, and spinal cord. Most cases (90%) are classified as sporadic ALS (sALS). The remainder 10% are inherited and referred to as familial ALS, and 2% of instances are due to mutations in Cu/Zn superoxide dismutase (SOD1). Using cDNA microarray on postmortem spinal cord specimens of four sALS patients compared to four age-matched nonneurological controls, we found major changes in the expression of mRNA in 60 genes including increase of cathepsin B and cathepsin D (by the factors 2 and 2.3, respectively), apolipoprotein E (Apo E; factor 4.2), epidermal growth factor receptor (factor 10), ferritin (factor 2), and lysosomal trafficking regulator (factor 10). The increase in the expression of these genes was verified by quantitative reverse transcriptase polymerase chain reaction. Further analysis of these genes in hSOD1-G93A transgenic mice revealed increase in the expression in parallel with the deterioration of motor functions quantified by means of rotorod performance. The comparability of the findings in sALS patients and in the hSOD1-G93A transgenic mouse model suggests that the examined genes may play a specific role in the pathogenesis of ALS.

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Acknowledgments

The project was partially supported by the National Parkinson Foundation, Miami, FL, USA; the Norma and Alan Aufzein Chair for Research in Parkinson’s disease, Tel Aviv University, Israel; and the Scientific and Technical Cooperation Austria–Israel, project #III/7 1999.

We are very grateful to Prof. Dr. Manfred Gerlach, Department of Clinical Neurochemistry, Medical Faculty, Würzburg, Germany, for providing us with spinal cord tissue of a patient who died from sALS.

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Authors and Affiliations

  1. Felsenstein Medical Research Center, Department of Neurology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Petah-Tikva, 49100, Israel

    Daniel Offen, Yael Barhum & Eldad Melamed

  2. Department of Pathology, Hospital for Nervous Diseases Wagner-Jauregg, 4020, Linz, Austria

    Norbert Embacher & Christoph Schindler

  3. Department of Neurology and Psychiatry, General Hospital, 4020, Linz, Austria

    Gerhard Ransmayr

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  1. Daniel Offen
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  2. Yael Barhum
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Correspondence to Daniel Offen.

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Offen, D., Barhum, Y., Melamed, E. et al. Spinal Cord mRNA Profile in Patients with ALS: Comparison with Transgenic Mice Expressing the Human SOD-1 Mutant. J Mol Neurosci 38, 85–93 (2009). https://doi.org/10.1007/s12031-007-9004-z

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  • DOI: https://doi.org/10.1007/s12031-007-9004-z

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