The response of denervated muscle to long-term stimulation (1985, revisited here in 2014)

Abstract

In 1985, at a meeting in Abano, I presented results showing that direct stimulation of skeletal muscles with appropriate stimulus patterns prevents the effects of denervation on non-junctional properties of muscle fibers. Hence, it appeared unnecessary to postulate that unknown nerve-derived trophic factors control such properties, as posited by the (anterograde) neurotrophic hypothesis. Here I discuss this conclusion in the light of what we know today, particularly with respect to the many lines of evidence that were then taken to support the trophic hypothesis, but which today have alternative interpretations consistent with control by evoked impulse activity. Despite much effort, no one has yet identified any nerve-derived factor consistent with the neurotrophic hypothesis. Reports favoring the existence of neurotrophic factors were numerous before 2000. Now they have essentially disappeared from the literature, including original research papers, textbooks and handbooks, suggesting that the hypothesis is no longer arguable. Thus, the results that I presented in our paper in 1985 seem to have held up rather well.

Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen

“…The important factor is not the age per se , or the kind of activity the senior recreational sportsmen performed, but the amount of activations/contractions during the previous many decades. Taking into account that slow motoneurons are active at least 20 times more often per day than the fast motoneurons, 54,55 in both everyday life and in sports activities, it is this higher-level of activity that is most likely to maintain motoneuron axons, muscle fibers and their MHC content. 17,20,29 Our working hypothesis is that the muscle fibers co-expressing fast and slow MHCs contribute to the process of slow type transformation and clustering as random events that can’t be interpreted as the result of the synchronous transformation of the whole fibers belonging to a motor unit, nothing to say to the large motor units in muscles of the cohort of senior recreational sportsmen, a mechanism that is well known to occur in cross-reinnervation models 13,45 , while it is more presumed than demonstrated after volitional exercise.…”

Muscle spindles of the rat sternomastoid muscle

“…17-19 Yellin representative of those motor units most readily recruited and thus most frequently used during less than maximal efforts. 15,20 Evidence of substantial difference in daily activation of slow and fast motor units was also sumarized by Terje Lømo in a recent review, 21 discussing his pioneering Nature 1985 paper. 22 Thus, muscle spindles are preferentially located within the muscle in order to meet precise regulatory functions in those motor units that are frequently active and thus need frequent and fine regulation by the muscle spindles trough the Sternomastoid nerve (Figure 3).…”

Myokines in Home-Based Functional Electrical Stimulation-Induced Recovery of Skeletal Muscle in Elderly and Permanent Denervation

“…39-42 This is mainly related to the undetermined molecular nature of the trophic factors released by motor neurons to the muscle fibers of the different types of motor units. 43 It is well known that such mechanisms contribute to neuromuscular junction development and maintenance; however, if and what chemical trophic factors influence the synchronized expression of the hundreds of nuclei belonging to a single muscle fiber remains a subject of hypotheses, while the synchronized spread of muscle action potential seems to be a more rational mechanism. 43 Two reviews provide an excellent summary of what is known or hypothesized about this subject.…”

“…43 It is well known that such mechanisms contribute to neuromuscular junction development and maintenance; however, if and what chemical trophic factors influence the synchronized expression of the hundreds of nuclei belonging to a single muscle fiber remains a subject of hypotheses, while the synchronized spread of muscle action potential seems to be a more rational mechanism. 43 Two reviews provide an excellent summary of what is known or hypothesized about this subject. 1,44 It is well established that physical exercise and dietary proteins, as well as the intake of specific amino acids, are able to counteract the processes related to the progression of muscle mass loss.…”