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Increased ROS Level in Spinal Cord of Wobbler Mice due to Nmnat2 Downregulation

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Abstract

Amyotrophic lateral sclerosis is a devastating motor neuron disease and to this day not curable. While 5–10% of patients inherit the disease (familiar ALS), up to 95% of patients are diagnosed with the sporadic form (sALS). ALS is characterized by the degeneration of upper motor neurons in the cerebral cortex and of lower motor neurons in the brainstem and spinal cord. The wobbler mouse resembles almost all phenotypical hallmarks of human sALS patients and is therefore an excellent motor neuron disease model. The motor neuron disease of the wobbler mouse develops over a time course of around 40 days and can be divided into three phases: p0, presymptomatic; p20, early clinical; and p40, stable clinical phase. Recent findings suggest an essential implication of the NAD+-producing enzyme Nmnat2 in neurodegeneration as well as maintenance of healthy axons. Here, we were able to show a significant downregulation of both gene and protein expression of Nmnat2 in the spinal cord of the wobbler mice at the stable clinical phase. The product of the enzyme NAD+ is also significantly reduced, and the values of the reactive oxygen species are significantly increased in the spinal cord of the wobbler mouse at p40. Thus, the deregulated expression of Nmnat2 appears to have a great influence on the cellular stress in the spinal cord of wobbler mice.

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Acknowledgements

The authors gratefully acknowledge A. Lodwig, C. Grzelak, and S. Wenderdel for technical assistance, as well as A. Lenz for secretarial work. This research was supported by FoRUM - F874N-2016 (Ruhr-University Bochum).

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Authors and Affiliations

  1. Institute of Anatomy, Department of Cytology, Ruhr University Bochum, 44801, Bochum, Germany

    Pascal Röderer, Lara Klatt, Felix John, Verena Theis, Carsten Theiss & Veronika Matschke

  2. Institute of Biochemistry and Pathobiochemistry, Department of Molecular Cell Biology, Ruhr University Bochum, 44801, Bochum, Germany

    Konstanze F. Winklhofer

  3. Institute of Anatomy, Department of Cytology, Ruhr University Bochum, Universitätsstr. 150, Building MA 5/52, 44780, Bochum, Germany

    Veronika Matschke

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  1. Pascal Röderer
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Röderer, P., Klatt, L., John, F. et al. Increased ROS Level in Spinal Cord of Wobbler Mice due to Nmnat2 Downregulation. Mol Neurobiol 55, 8414–8424 (2018). https://doi.org/10.1007/s12035-018-0999-7

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