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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

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).
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f3: 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).

Mentions: To test the hypothesis that increased NMJ fragmentation per se is associated with a decline in the efficacy of neuromuscular transmission, we looked to see whether key measures of neuromuscular transmission at individual NMJs (EPC amplitude, QC, QC/μm2), independent of the age of the animal, were significantly correlated with the number of fragments. In each case there was a positive correlation, implying enhanced (rather than impaired) transmission with age, but in no case was the correlation statistically significant (Fig. 3).


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)

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

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

f3: 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).
Mentions: To test the hypothesis that increased NMJ fragmentation per se is associated with a decline in the efficacy of neuromuscular transmission, we looked to see whether key measures of neuromuscular transmission at individual NMJs (EPC amplitude, QC, QC/μm2), independent of the age of the animal, were significantly correlated with the number of fragments. In each case there was a positive correlation, implying enhanced (rather than impaired) transmission with age, but in no case was the correlation statistically significant (Fig. 3).

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