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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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TTX block enhances synaptic transmission. (A) Inset, representative recordings of MEPPs from an FDB muscle fiber of a WldS mouse, after 7 days preconditioning, unilateral sciatic nerve block. MEPP amplitude was significantly increased but, interestingly, not as substantially as in remaining innervated fibers 7 days after axotomy, rather than nerve block (P < 0.01; ANOVA/Bonferroni comparing all three groups). Neither MEPP frequency (B) nor EPP rise time (C) was significantly affected by nerve block. However, EPP half-decay time (D), EPP amplitude (E), and quantal content (F) were all significantly increased (P < 0.05; t-tests in each case). Graphs show mean ± S.E.M., n = 3–9 muscles in each group. Single asterisks, P < 0.05; double asterisks: P < 0.01).
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f0045: TTX block enhances synaptic transmission. (A) Inset, representative recordings of MEPPs from an FDB muscle fiber of a WldS mouse, after 7 days preconditioning, unilateral sciatic nerve block. MEPP amplitude was significantly increased but, interestingly, not as substantially as in remaining innervated fibers 7 days after axotomy, rather than nerve block (P < 0.01; ANOVA/Bonferroni comparing all three groups). Neither MEPP frequency (B) nor EPP rise time (C) was significantly affected by nerve block. However, EPP half-decay time (D), EPP amplitude (E), and quantal content (F) were all significantly increased (P < 0.05; t-tests in each case). Graphs show mean ± S.E.M., n = 3–9 muscles in each group. Single asterisks, P < 0.05; double asterisks: P < 0.01).

Mentions: We found no significant effect of TTX block on FDB muscle fiber resting membrane potential (TTX-blocked; −67.33 ± 2.38 mV, n = 5; saline control: −71.59 ± 2.38 mV, n = 3; P > 0.05, t-test). FDB muscles from WldS mice without conditioning nerve block showed a mean MEPP amplitude of 1.08 ± 0.12 mV (n = 5; Fig. 9A). Seven days of nerve block caused a significant, approximately 50% increase in MEPP amplitude (1.58 ± 0.12 mV, n = 9). However, this increase was less than that observed 7 days after complete axotomy (2.55 ± 0.47 mV, n = 3 respectively, P < 0.01 ANOVA; Bonferroni post hoc; compared with Ribchester et al., 1995).


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)

TTX block enhances synaptic transmission. (A) Inset, representative recordings of MEPPs from an FDB muscle fiber of a WldS mouse, after 7 days preconditioning, unilateral sciatic nerve block. MEPP amplitude was significantly increased but, interestingly, not as substantially as in remaining innervated fibers 7 days after axotomy, rather than nerve block (P < 0.01; ANOVA/Bonferroni comparing all three groups). Neither MEPP frequency (B) nor EPP rise time (C) was significantly affected by nerve block. However, EPP half-decay time (D), EPP amplitude (E), and quantal content (F) were all significantly increased (P < 0.05; t-tests in each case). Graphs show mean ± S.E.M., n = 3–9 muscles in each group. Single asterisks, P < 0.05; double asterisks: P < 0.01).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4362769&req=5

f0045: TTX block enhances synaptic transmission. (A) Inset, representative recordings of MEPPs from an FDB muscle fiber of a WldS mouse, after 7 days preconditioning, unilateral sciatic nerve block. MEPP amplitude was significantly increased but, interestingly, not as substantially as in remaining innervated fibers 7 days after axotomy, rather than nerve block (P < 0.01; ANOVA/Bonferroni comparing all three groups). Neither MEPP frequency (B) nor EPP rise time (C) was significantly affected by nerve block. However, EPP half-decay time (D), EPP amplitude (E), and quantal content (F) were all significantly increased (P < 0.05; t-tests in each case). Graphs show mean ± S.E.M., n = 3–9 muscles in each group. Single asterisks, P < 0.05; double asterisks: P < 0.01).
Mentions: We found no significant effect of TTX block on FDB muscle fiber resting membrane potential (TTX-blocked; −67.33 ± 2.38 mV, n = 5; saline control: −71.59 ± 2.38 mV, n = 3; P > 0.05, t-test). FDB muscles from WldS mice without conditioning nerve block showed a mean MEPP amplitude of 1.08 ± 0.12 mV (n = 5; Fig. 9A). Seven days of nerve block caused a significant, approximately 50% increase in MEPP amplitude (1.58 ± 0.12 mV, n = 9). However, this increase was less than that observed 7 days after complete axotomy (2.55 ± 0.47 mV, n = 3 respectively, P < 0.01 ANOVA; Bonferroni post hoc; compared with Ribchester et al., 1995).

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