Degeneration of Neuromuscular Junction in Age and Dystrophy

Abstract

Functional denervation is a hallmark of aging sarcopenia as well as of muscular dystrophy. It is thought to be a major factor reducing skeletal muscle mass, particularly in the case of sarcopenia. Neuromuscular junctions (NMJs) serve as the interface between the nervous and skeletal muscular systems, and thus they may receive pathophysiological input of both pre- and post-synaptic origin. Consequently, NMJs are good indicators of motor health on a systemic level. Indeed, upon sarcopenia and dystrophy, NMJs morphologically deteriorate and exhibit altered characteristics of primary signaling molecules, such as nicotinic acetylcholine receptor and agrin. Since a remarkable reversibility of these changes can be observed by exercise, there is significant interest in understanding the molecular mechanisms underlying synaptic deterioration upon aging and dystrophy and how synapses are reset by the aforementioned treatments. Here, we review the literature that describes the phenomena observed at the NMJ in sarcopenic and dystrophic muscle as well as to how these alterations can be reversed and to what extent. In a second part, the current information about molecular machineries underlying these processes is reported.

Multiple roles of integrin-α3 at the neuromuscular junction

“…6F,L; 7.70-fold increase over that of WT at 2 months, P=0.027; 1.8-fold increase over that of WT at 10 months, P=0.025). These specific structural alterations have been commonly reported in aged (20-26 month old) mice (Li et al, 2011;Rudolf et al, 2014;Valdez et al, 2010) and in models of neurodegeneration (Park, 2015). Interestingly, we observed that these changes progressively accumulated in both WT and mutant mice between 2 and 10 months of age, but that the incidence of these was greater in mutants at both time points (with the exception of varicose nerve terminals, Fig.…”

“…(∼2 year old) mice (Li et al, 2011;Rudolf et al, 2014), and in models of neurodegeneration such as amyotrophic lateral sclerosis (ALS) (Park, 2015), even at 2 months of age (Fig. 6).…”

Cardiac troponin T and fast skeletal muscle denervation in ageing

“…It decreases quality of life in older adults and renders an increasingly heavy burden on the healthcare system. Ageing skeletal muscle undergoes chronic denervation, and the NMJ, the key structure that connects motor neuron nerves with muscle cells, shows increased deterioration in structure and function with ageing 26, 27. Previous studies have shown that with ageing, type II fast‐twitch skeletal muscle fibres atrophy more than type I slow‐twitch fibres across multiple species 28, 29, 30.…”

Lung Vital Capacity of Choir Singers and Nonsingers: A Comparative Study

“…The increasing number of presynaptic vesicles increases the amount of acetylcholine. 12,13 There is some research which discussed the effect of doing sports on lung vital capacity. A study in people who attend yoga class found an increasing vital capacity in people who do yoga class regularly.…”