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Differential skeletal muscle gene expression after upper or lower motor neuron transection

  • Muscle Physiology
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Abstract

Causes of disuse atrophy include loss of upper motor neurons, which occurs in spinal cord injury (SCI) or lower motor neurons (denervation). Whereas denervation quickly results in muscle fibrillations, SCI causes delayed onset of muscle spasticity. To compare the influence of denervation or SCI on muscle atrophy and atrophy-related gene expression, male rats had transection of either the spinal cord or sciatic nerve and were sacrificed 3, 7, or 14 days later. Rates of atrophy increased gradually over the first week after denervation and then were constant. In contrast, atrophy after SCI peaked at 1 week, then declined sharply. The greater atrophy after SCI compared to denervation was preceded by high levels of ubiquitin ligase genes, MAFbx and MuRF1, which then also markedly declined. After denervation, however, expression of these genes remained elevated at lower levels throughout the 2-week time course. Interestingly, expression of the muscle growth factor, IGF-1 was increased at 3 days after denervation when fibrillation also peaks compared to SCI. Expression of IGF-1R, GADD45, myogenin, and Runx1 were also initially increased after denervation or SCI, with later declines in expression levels which correlated less well with rates of atrophy. Thus, there were significant time-dependent differences in muscle atrophy and MAFbx, MuRF1, and IGF-1 expression following SCI or denervation which may result from distinct temporal patterns of spontaneous muscle contractile activity due to injury to upper versus lower motor neurons.

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Acknowledgements

This work was supported by Veterans Health Administration, Rehabilitation Research and Development Service (B4162C to WAB, B3347K to CC), and United Spinal Association (to WAB).

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Authors and Affiliations

  1. Department of Veterans Affairs, Center of Excellence for the Medical Consequences of SCI, James J. Peters VA Medical Center, Bronx, New York, NY, 10468, USA

    Jingbo Zhao, Yuangfei Zhang, Weidong Zhao, Yong Wu, Jiangping Pan, William A. Bauman & Christopher Cardozo

  2. Department of Medicine, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY, 10029, USA

    Jingbo Zhao, William A. Bauman & Christopher Cardozo

  3. Department of Rehabilitation Medicine, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY, 10029, USA

    William A. Bauman & Christopher Cardozo

  4. Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, NY, 10595, USA

    Richard J. Zeman & Xialing Wen

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Zeman, R.J., Zhao, J., Zhang, Y. et al. Differential skeletal muscle gene expression after upper or lower motor neuron transection. Pflugers Arch - Eur J Physiol 458, 525–535 (2009). https://doi.org/10.1007/s00424-009-0643-5

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