Activity-dependent degeneration of axotomized neuromuscular synapses in Wld S mice.
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.
Affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Hugh Robson Building, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.Show MeSH
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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).
Affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, Hugh Robson Building, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.