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

Willadt S, Nash M, Slater CR - Sci Rep (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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f1: 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).

Mentions: There was no obvious qualitative difference between the appearance of the NMJs from middle-aged and old mice (Fig. 1a,b). As a result, during subsequent ‘blind’ analysis of NMJ structure, it was not possible to tell which NMJs were from old mice and which were from middle-aged ones (see Methods). Nonetheless, analysis of the number of fragments of AChR-rich membrane at individual NMJs revealed a significant increase of about 27% in the average number of fragments in the old animals (Table 1). This corresponded to an average increase of about 1.5 fragments at each NMJ (from 5.6 to 7.1). Particularly noticeable was the appearance in the old mice of a substantial number of NMJs with 10 or more fragments (Fig. 1c). These represented only 2.6% (1/38) of NMJs in middle-aged mice but 22% (9/41) in old mice. We conclude that a significant increase in the number of fragments must have occurred at these NMJs after 1 year of age.


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

Willadt S, Nash M, Slater CR - Sci Rep (2016)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837408&req=5

f1: 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).
Mentions: There was no obvious qualitative difference between the appearance of the NMJs from middle-aged and old mice (Fig. 1a,b). As a result, during subsequent ‘blind’ analysis of NMJ structure, it was not possible to tell which NMJs were from old mice and which were from middle-aged ones (see Methods). Nonetheless, analysis of the number of fragments of AChR-rich membrane at individual NMJs revealed a significant increase of about 27% in the average number of fragments in the old animals (Table 1). This corresponded to an average increase of about 1.5 fragments at each NMJ (from 5.6 to 7.1). Particularly noticeable was the appearance in the old mice of a substantial number of NMJs with 10 or more fragments (Fig. 1c). These represented only 2.6% (1/38) of NMJs in middle-aged mice but 22% (9/41) in old mice. We conclude that a significant increase in the number of fragments must have occurred at these NMJs after 1 year of age.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Novartis Institutes for Biomedical Research, Basel, Switzerland.

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.

No MeSH data available.


Related in: MedlinePlus