Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 294, Issue 1-2, Pages 95-101Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2010.03.022
Keywords
Amyotrophic lateral sclerosis (ALS); Motor neuron disease (MND); Muscle atrophy; Neuronal nitric oxide synthase (nNOS); Superoxide dismutase (SOD1)
Categories
Funding
- Nervous and Mental disorders [20B-13]
- Research on Measures for Intractable Diseases
- Japanese Ministry of Health Labor and Welfare [19590977, 21591070]
- Japanese Ministry of Education, Culture, Sports, Science and Technology [19890016]
- Grants-in-Aid for Scientific Research [21591070, 19890016, 19590977] Funding Source: KAKEN
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Previously, we demonstrated that neuronal nitric oxide synthase (nNOS) is activated and promotes muscle atrophy in skeletal muscle during tail suspension, a model of unloading and denervation. Here, we examined patients with amyotrophic lateral sclerosis (ALS) and mutant (H46R) SOD1 transgenic (Tg) mice model using immunohistochemistry, Western blotting and real time PCR. We found cytoplasmic nNOS staining of angulated muscle fibers in patients with ALS. We also examined mutant SOD1 Tg mice and found cytoplasmic nNOS staining even before the onset of clinical muscle atrophy. In the Tg mice, nNOS was largely extracted with 100 mM NaCl and barely detected in the pellet fraction, suggesting fragile anchoring of nNOS to the sarcolemma. We also showed an elevated expression of atrogin-1, key molecules in muscle atrophy at the end stage. A common nNOS dislocation/atrogin-1/muscle atrophy pathway among tail suspension, denervation and ALS is suggested. nNOS modulation therapy may be beneficial in several types of muscle atrophy. (C) 2010 Elsevier B.V. All rights reserved.
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