Age changes of neuromuscular junctions in the extensor digitorum longus muscle of spontaneous thymoma BUF/Mna rats

Abstract

BUF/Mna rats spontaneously develop thymomas and cause muscle weakness of hind legs at an advanced age. This rat strain has been recognized as a suitable animal model for human myasthenia gravis or related myopathies. To characterize the structural changes of neuromuscular junctions (NMJs) in BUF/Mna rats, subneural apparatuses (SNAs) of extensor digitorum longus muscles of young-adult (4-month-old) and aged (22- to 25-month-old) male rats were examined using scanning and transmission electron microscopy. The SNAs of NMJs in young rats consist of complex labyrinthine gutters with numerous slit-like junctional folds. SNAs in aged BUF/Mna rats, however, are characterized by: (1) a group of cup-like depressions with very wide slit-like junctional folds in relatively large muscle fibers (the major type), (2) the presence of slit-like folds on the flat sarcoplasm outside the cup-like depressions or on the protruded sarcoplasm, and (3) winding gutters or a small number of round depressions with poorly developed synaptic folds in small and medium-sized muscle fibers (the minor type). Since similar structural changes have been reported in dystrophic mice or normally aged rats, it is suggested that both the slowly progressing muscle atrophy and age-dependent turnover of muscle fibers may occur in the aged BUF/Mna rats.

Muscle weakness and neuromuscular junctions in aging and disease

“…8). 38 Our studies of MG with MuSK antibodies showed that the structure of NMJ is not statically maintained; rather, the nerve‐to muscle and muscle‐to‐nerve signals stimulate dynamic assembly and disassembly of NMJ's molecular complexes. A steady flow of molecular complexes at NMJ sustains both the structures and functions of the motor system, including motoneurons and muscles.…”

Thymoma related myasthenia gravis in humans and potential animal models

“…Indeed, thymomas have been described in a variety of animals, both mammals and birds. Among mammals, thymomas develop almost consistently in inbred BUF/Mna rats [92][93][94], but rarely in other rat strains and wild rats [95], except for Praomys (Mastomys) natalensis that shows thymomas in up to 30%…”

The important role of the neuromuscular junction in maintaining muscle mass and strength

“…Anatomical studies in laboratory animals have shown that, in aged muscles, some presynaptic nerves exhibit terminal sprouts, and that postsynaptic AChR clusters are often fragmented into lots of small islands instead of a typical pretzel-like structure; however, these structures are rarely observed at NMJs in young adult muscles [6][7][8][9][10] . In addition, electron microscopic study has shown that labyrinthine synaptic gutters observed at young adult NMJs become simplified into a number of cup-like depressions at aged NMJs 11) . On the presynaptic side, it has been shown that the number of active zones and the expression level of Bassoon, a scaffold protein essential for assembly of the active zone, was significantly reduced at the nerve terminals of NMJs in aged mice 12,13) .…”