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. 2016 Apr 20:6:24849.
doi: 10.1038/srep24849.

Age-related fragmentation of the motor endplate is not associated with impaired neuromuscular transmission in the mouse diaphragm

Silvia Willadt  1 , Mark Nash  1 , Clarke R Slater  2
Affiliations

Age-related fragmentation of the motor endplate is not associated with impaired neuromuscular transmission in the mouse diaphragm

Silvia Willadt et al. Sci Rep. .

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.

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Conflict of interest statement

S.W. and M.N. are employees of Novartis Pharma, A.G. C.R.S declares no competing financial interest.

Figures

Figure 1
Figure 1. Appearance of NMJs in middle-aged and old mice.
(a) Images of middle-aged NMJs (top: 6 fragments, bottom: 7 fragments). (b) Images of old NMJs (top: 11 fragments, bottom: 10 fragments). Scale bar = 12.5 μm. (c) cumulative histograms of the number of fragments present at NMJs in middle-aged mice (solid symbols) and old mice (open symbols).
Figure 2
Figure 2. Evoked release at diaphragm NMJs in middle-aged and old mice.
(a) Comparison of mean EPC Amplitude between middle-aged and old animals; P = 0.001. (b) Comparison of mean quantal content between middle-aged and old animals. P > 0.05.Values show mean ± SEM.
Figure 3
Figure 3. Evoked release at mouse diaphragm NMJs containing different numbers of fragments.
Solid symbols, middle-aged mice; open symbols, old mice. The slope of the least-squares trend line does not differ significantly from zero for any of the three measures of release (in all cases n = 82, correl. coeff. < 0.19, p ≥ 0.1).
See this image and copyright information in PMC

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