Abstract
Action potential is transmitted to muscle fibers through specialized synaptic interfaces called neuromuscular junctions (NMJs). These structures are capped by terminal Schwann cells (tSCs), which play essential roles during formation and maintenance of the NMJ. tSCs are implicated in the correct communication between nerves and muscles, and in reinnervation upon injury. During aging, loss of muscle mass and strength (sarcopenia and dynapenia) are due, at least in part, to the progressive loss of contacts between muscle fibers and nerves. Despite the important role of tSCs in NMJ function, very little is known on their implication in the NMJ-aging process and in age-associated denervation. This review summarizes the current knowledge about the implication of tSCs in the age-associated degeneration of NMJs. We also speculate on the possible mechanisms underlying the observed phenotypes.
Highlights
The neuromuscular junction (NMJ) is the synaptic interface through which motor neurons innervate muscle fibers [1, 2]
The NMJ presents a characteristic pretzel-like structure [14] which is composed of five essential elements: (i) presynaptic motor nerve terminals; (ii) postsynaptic endplates in muscle fiber membranes; (iii) basal lamina, the extracellular matrix located in the synaptic cleft [20, 21]; (iv) terminal Schwann cells, which cover the nerve-muscle junctions (2-5 tSCs per NMJ) [22, 23], and (v) fibroblast-like cells known as kranocytes or perisynaptic fibroblasts, which cap the NMJs from above the tSCs, covering the end-plate area in its entirety
Prevention and treatment of sarcopenia and dynapenia have emerged as fields of high medical need in order to improve the quality of life of the elderly people
Summary
The neuromuscular junction (NMJ) is the synaptic interface through which motor neurons innervate muscle fibers [1, 2]. Since tSCs are essential in maintaining the structure and function of NMJs and play key roles as sensors of synaptic communication and during NMJ-reinnervation, we believe that analyzing the signaling pathways affected in age-related degeneration is of utmost importance. Similar tSC-plasticity and nerve-migration has been observed in ALS mouse models [36] and during aging [15]; the NRG-pathway could be implicated in the denervation-reinnervation cycle in aged-NMJs through its regulatory role in tSCs. NRGs may be essential for maintaining clustered-AChRs during aging, and the correct expression of NRG in tSCs could be necessary for the regulation of cell sprouting and migration during denervation-reinnervation process in aged muscles. Since both CD44 and ErbB are important regulators of morphological plasticity and cell migration [142,143,144,145, 149,150,151,152], the NRG-ErbB-CD44 axis may be involved in the regulation of tSC morphological plasticity, migration and phenotypic stability during adulthood and aging
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