Abstract
As mammals age, their neuromuscular junctions (NMJs) gradually change their form, acquiring an increasingly fragmented appearance consisting of numerous isolated regions of synaptic differentiation. It has been suggested that this remodelling is associated with impairment of neuromuscular transmission, and that this contributes to age-related muscle weakness in mammals, including humans. The underlying hypothesis, that increasing NMJ fragmentation is associated with impaired transmission, has never been directly tested. Here, by comparing the structure and function of individual NMJs, we show that neuromuscular transmission at the most highly fragmented NMJs in the diaphragms of old (26–28 months) mice is, if anything, stronger than in middle-aged (12–14 months) mice. We suggest that NMJ fragmentation per se is not a reliable indicator of impaired neuromuscular transmission.
Highlights
As a result, during subsequent ‘blind’ analysis of neuromuscular junction (NMJ) structure, it was not possible to tell which NMJs were from old mice and which were from middle-aged ones
Analysis of the number of fragments of acetylcholine receptors (AChRs)-rich membrane at individual NMJs revealed a significant increase of about 27% in the average number of fragments in the old animals (Table 1)
We conclude that a significant increase in the number of fragments must have occurred at these NMJs after 1 year of age
Summary
We have compared NMJs from mice of 2 ages, 12–14 months and [24,25,26,27,28] months These are similar to the ages studied by a number of other authors as representing ‘adult’ and ‘aged’ rats and mice[6,13,17,18]. We took our observations from 1 year-old mice as a reference against which to compare values from the older mice. Our findings confirm those from earlier comparisons of the structure and function of populations of NMJs: we find no decline, and even some evidence of an enhancement, of key features of neuromuscular transmission with increasing NMJ fragmentation. We conclude that NMJ fragmentation per se does not imply a decline in fundamental features of transmission
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