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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 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.
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f2: 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.

Mentions: There was no significant difference between middle-aged and old mice in the amplitude or frequency of the spontaneous miniature endplate potentials/currents (mEPPs/mEPCs) which result from the action of individual transmitter quanta on the muscle fiber membrane (Table 1). However, the amplitudes of the EPCs evoked by nerve stimulation at 1 Hz were significantly larger in the old mice (Fig. 2a, Table 1) (−113.1 nA in middle-aged vs −149.2 nA in old mice, p = 0.001), confirming previous findings cited above. In our sample, although the average QC was about 15% bigger in the old mice than in the middle-aged ones, this difference was not statistically significant (p = 0.09) (Fig. 2b, Table 1). Neither was there any significant difference in the QC/area (0.20 quanta/μm2 in middle-aged vs 0.22 in old mice, p = 0.25) as might be expected if the nerve terminal in old mice occupied a smaller fraction of the postsynaptic area then in middle-aged mice.


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

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

f2: 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.
Mentions: There was no significant difference between middle-aged and old mice in the amplitude or frequency of the spontaneous miniature endplate potentials/currents (mEPPs/mEPCs) which result from the action of individual transmitter quanta on the muscle fiber membrane (Table 1). However, the amplitudes of the EPCs evoked by nerve stimulation at 1 Hz were significantly larger in the old mice (Fig. 2a, Table 1) (−113.1 nA in middle-aged vs −149.2 nA in old mice, p = 0.001), confirming previous findings cited above. In our sample, although the average QC was about 15% bigger in the old mice than in the middle-aged ones, this difference was not statistically significant (p = 0.09) (Fig. 2b, Table 1). Neither was there any significant difference in the QC/area (0.20 quanta/μm2 in middle-aged vs 0.22 in old mice, p = 0.25) as might be expected if the nerve terminal in old mice occupied a smaller fraction of the postsynaptic area then in middle-aged mice.

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