Yesterday's post focused on the utility of neuronal nitric oxide synthase (nNOS) histochemisty in muscle biopsies. Dr. Steve Moore, who was also featured yesterday, kindly sent me a link to an article by a fellow University of Iowa faculty member, Dr. Kevin Campbell (pictured with his lab staff) and colleagues. Recently published in Nature, the article is titled: Sarcolemma-localized nNOS is required to maintain activity after mild exercise.
Campbell and colleagues address the phenomenon of exaggerated muscle fatigue after exercise, a finding present in many neuromuscular disorders. Using mouse models, the Campbell lab showed that sarcolemma-localized signalling by nNOS in skeletal muscle is required to maintain activity after mild exercise. To quote the abstract: "We show that nNOS-null mice do not have muscle pathology and have no loss of muscle-specific force after exercise but do display this exaggerated fatigue response to mild exercise.... Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction-induced signalling from sarcolemma-localized nNOS, which decreases cGMP-mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise-induced signalling." It is interesting that there was no histomorphological pathology in the nNOS-null mice, suggesting that nNOS histochemical staining of patient biopsies might reveal an underlying disease process in otherwise non-specific biopsy findings. Or, as Steve Moore put it, nNOS can function as the "canary in the mine" for detecting myopathies.
I discuss issues pertaining to the practice of neuropathology -- including nervous system tumors, neuroanatomy, neurodegenerative disease, muscle and nerve disorders, ophthalmologic pathology, neuro trivia, neuropathology gossip, job listings and anything else that might be of interest to a blue-collar neuropathologist.
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hey - thanks for commenting....I happen to LOVE neurologists!! okay, that sounds weird, but my husband had a craniopharyngioma removed trasphenoidally in 1999 so we've spent alot of time with neurologists/endocrinologists/neuropsychologists. His pituitary was destroyed and he experienced significant permanent memory loss, problems with sequencing (and maybe some judgment....or maybe it's just his male-ness :), and loss of peripheral vision. Anyway, I thought it was funny when I popped over to your blog and saw the connection....
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