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Activity-dependent degeneration of axotomized neuromuscular synapses in Wld S mice.

Brown R, Hynes-Allen A, Swan AJ, Dissanayake KN, Gillingwater TH, Ribchester RR - Neuroscience (2015)

Bottom Line: Periodic high-frequency nerve stimulation (100 Hz: 1s/100s) reduced synaptic protection in Wld(S) preparations by about 50%.This effect was abolished in reduced Ca(2+) solutions.Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity.

View Article: PubMed Central - PubMed

Affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Hugh Robson Building, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.

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Synaptic degeneration in axotomized WldS mouse muscles is asynchronous. (A) Whole-mount montage of a thy1.2YFP16:WldS mouse DL muscle, 5 days after cutting the tibial nerve. YFP fluorescence (green) and TRITC-α-BTX (red) counterstaining of AChR at motor endplates shows many NMJ were still fully occupied (B). Partially occupied (C, D) and vacant (denervated) endplates (E) were also readily discernible. Scale bar in E applies to images B–E. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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f0010: Synaptic degeneration in axotomized WldS mouse muscles is asynchronous. (A) Whole-mount montage of a thy1.2YFP16:WldS mouse DL muscle, 5 days after cutting the tibial nerve. YFP fluorescence (green) and TRITC-α-BTX (red) counterstaining of AChR at motor endplates shows many NMJ were still fully occupied (B). Partially occupied (C, D) and vacant (denervated) endplates (E) were also readily discernible. Scale bar in E applies to images B–E. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Mentions: As our initial benchmark, we first established the pattern of innervation of toe muscles in WldS mice 5 days after axotomy in vivo, utilizing co-expression of the thy1.2-YFP transgene as a reporter. Whole-mounts of DL muscles showed a pattern of fully occupied, partially occupied and vacant motor endplates, suggesting that degeneration occurs asynchronously within the population of NMJs (Fig. 2). Quantitative scoring of endplate occupancy and functional responses in thy1.2YFP16:WldS mice showed that about 25–50% of endplates were denervated by 5 days post axotomy, which is a similar incidence at that time point to immunostained material (Gillingwater et al., 2002; Bridge et al., 2009). Inspection of single axotomized motor units in thy1.2YFPH:WldS mice, in which only about 5% of motor neurons express YFP, revealed occupied and partially vacated endplates within the same motor unit (Fig. 3), suggesting that synaptic retraction occurs asynchronously even within motor units and may therefore be locally regulated (Keller-Peck et al., 2001; Gillingwater and Ribchester, 2003).


Activity-dependent degeneration of axotomized neuromuscular synapses in Wld S mice.

Brown R, Hynes-Allen A, Swan AJ, Dissanayake KN, Gillingwater TH, Ribchester RR - Neuroscience (2015)

Synaptic degeneration in axotomized WldS mouse muscles is asynchronous. (A) Whole-mount montage of a thy1.2YFP16:WldS mouse DL muscle, 5 days after cutting the tibial nerve. YFP fluorescence (green) and TRITC-α-BTX (red) counterstaining of AChR at motor endplates shows many NMJ were still fully occupied (B). Partially occupied (C, D) and vacant (denervated) endplates (E) were also readily discernible. Scale bar in E applies to images B–E. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362769&req=5

f0010: Synaptic degeneration in axotomized WldS mouse muscles is asynchronous. (A) Whole-mount montage of a thy1.2YFP16:WldS mouse DL muscle, 5 days after cutting the tibial nerve. YFP fluorescence (green) and TRITC-α-BTX (red) counterstaining of AChR at motor endplates shows many NMJ were still fully occupied (B). Partially occupied (C, D) and vacant (denervated) endplates (E) were also readily discernible. Scale bar in E applies to images B–E. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Mentions: As our initial benchmark, we first established the pattern of innervation of toe muscles in WldS mice 5 days after axotomy in vivo, utilizing co-expression of the thy1.2-YFP transgene as a reporter. Whole-mounts of DL muscles showed a pattern of fully occupied, partially occupied and vacant motor endplates, suggesting that degeneration occurs asynchronously within the population of NMJs (Fig. 2). Quantitative scoring of endplate occupancy and functional responses in thy1.2YFP16:WldS mice showed that about 25–50% of endplates were denervated by 5 days post axotomy, which is a similar incidence at that time point to immunostained material (Gillingwater et al., 2002; Bridge et al., 2009). Inspection of single axotomized motor units in thy1.2YFPH:WldS mice, in which only about 5% of motor neurons express YFP, revealed occupied and partially vacated endplates within the same motor unit (Fig. 3), suggesting that synaptic retraction occurs asynchronously even within motor units and may therefore be locally regulated (Keller-Peck et al., 2001; Gillingwater and Ribchester, 2003).

Bottom Line: Periodic high-frequency nerve stimulation (100 Hz: 1s/100s) reduced synaptic protection in Wld(S) preparations by about 50%.This effect was abolished in reduced Ca(2+) solutions.Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity.

View Article: PubMed Central - PubMed

Affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Hugh Robson Building, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.

Show MeSH
Related in: MedlinePlus