Nerve excitability changes related to axonal degeneration in amyotrophic lateral sclerosis: Insights from the transgenic SOD1G127X mouse model

Moldovan, Mihai; Alvarez, Susana; Pinchenko, V.; Marklund, Stefan L.; Graffmo, Karin S.; Krarup, Christian

doi:10.1016/j.expneurol.2011.11.008

Cited by 28 publications

(17 citation statements)

References 73 publications

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“…For example, studies with electrical stimulation of peripheral nerves have shown significant changes in the strength–duration rheobase and/or time constant in various neurodegenerative disorders (Farrar et al, 2011; Lin et al, 2011; Moldovan et al, 2012). The peripheral strength–duration rheobase and time constant are also affected by therapeutic interventions (Lin et al, 2011) and could therefore serve as putative biomarkers of therapeutic action to screen novel interventions.…”

Section: Introductionmentioning

confidence: 99%

Pulse width dependence of motor threshold and input–output curve characterized with controllable pulse parameter transcranial magnetic stimulation

Peterchev

Goetz

Westin

et al. 2013

Clinical Neurophysiology

134

185

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Objective To demonstrate the use of a novel controllable pulse parameter TMS (cTMS) device to characterize human corticospinal tract physiology. Methods Motor threshold and input-output (IO) curve of right first dorsal interosseus were determined in 26 and 12 healthy volunteers, respectively, at pulse widths of 30, 60, and 120 μs using a custom-built cTMS device. Strength–duration curve rheobase and time constant were estimated from the motor thresholds. IO slope was estimated from sigmoid functions fitted to the IO data. Results All procedures were well tolerated with no seizures or other serious adverse events. Increasing pulse width decreased the motor threshold and increased the pulse energy and IO slope. The average strength–duration curve time constant is estimated to be 196 μs, 95% CI [181 μs, 210 μs]. IO slope is inversely correlated with motor threshold both across and within pulse width. A simple quantitative model explains these dependencies. Conclusions Our strength–duration time constant estimate compares well to published values and may be more accurate given increased sample size and enhanced methodology. Multiplying the IO slope by the motor threshold may provide a sensitive measure of individual differences in corticospinal tract physiology. Significance Pulse parameter control offered by cTMS provides enhanced flexibility that can contribute novel insights in TMS studies.

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Section: Introductionmentioning

confidence: 99%

Pulse width dependence of motor threshold and input–output curve characterized with controllable pulse parameter transcranial magnetic stimulation

Peterchev

Goetz

Westin

et al. 2013

Clinical Neurophysiology

134

185

View full text Add to dashboard Cite

show abstract

“…This was at variance with observations from humans and cats (Moldovan & Krarup, ; Krarup & Moldovan, ) considering that recovery cycle is expected to change with membrane hyperpolarization (Kiernan & Bostock, ). Nevertheless, as previously discussed in detail (Moldovan et al ., ) in the mouse tibial nerve model, the recovery cycle is more ‘noisy’ due to the fact that the large secondary ‘F/H’ response confounds the tracking of the primary ‘M’ response during superexcitability.…”

Section: Discussionmentioning

confidence: 99%

“…The lower weight for strength–duration properties reflects the fact that rheobase cannot be modeled (the stimulus charge for 1 ms duration is conventionally 1). Also a lower weight was attributed for the recovery cycle, to account for both modeling uncertainties (Boërio et al ., ) as well as technical problems with recording the superexcitability in the mouse tibial nerve (Moldovan et al ., ). Overall, a satisfactory parameter optimization was considered when the discrepancy between the model fit and the measurements was reduced by more than 66% in both human and mouse optimizations.…”

Section: Methodsmentioning

confidence: 97%

Persistent alterations in active and passive electrical membrane properties of regenerated nerve fibers of man and mice

Moldovan

Alvarez

Rosberg

et al. 2015

Eur J of Neuroscience

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Excitability of regenerated fibers remains impaired due to changes in both passive cable properties and alterations in the voltage-dependent membrane function. These abnormalities were studied by mathematical modeling in human regenerated nerves and experimental studies in mice. In three adult male patients with surgically repaired complete injuries of peripheral nerves of the arm 22 months-26 years prior to investigation, deviation of excitability measures was explained by a hyperpolarizing shift in the resting membrane potential and an increase in the passive 'Barrett and Barrett' conductance (GBB) bridging the nodal and internodal compartments. These changes were associated with an increase in the 'fast' K(+) conductance and the inward rectifier conductance (GH). Similar changes were found in regenerated mouse tibial motor axons at 1 month after a sciatic crush lesion. During the first 5 months of regeneration, GH showed partial recovery, which paralleled that in GBB. The internodal length remained one-third of normal. Excitability abnormalities could be reversed by the energy-dependent Na(+)/K(+) pump blocker ouabain resulting in membrane depolarization. Stressing the Na(+) pumping system during a strenuous activity protocol triggered partial Wallerian degeneration in regenerated nerves but not in control nerves from age-matched mice. The current data suggest that the nodal voltage-gated ion channel machinery is restored in regenerated axons, although the electrical separation from the internodal compartment remains compromised. Due to the persistent increase in number of nodes, the increased activity-dependent Na(+) influx could lead to hyperactivity of the Na(+)/K(+) pump resulting in membrane hyperpolarization and neurotoxic energy insufficiency during strenuous activity.

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“…Nerve excitability changes have been also reported in pre-1124 symptomatic stages in mSOD G127X transgenic mice (Moldovan 1125(Moldovan et al, 2012.…”

Section: Q11mentioning

confidence: 91%

Amyotrophic lateral sclerosis: Current perspectives from basic research to the clinic

Mancuso

Navarro

2015

Progress in Neurobiology

102

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Nerve excitability changes related to axonal degeneration in amyotrophic lateral sclerosis: Insights from the transgenic SOD1G127X mouse model

Cited by 28 publications

References 73 publications

Pulse width dependence of motor threshold and input–output curve characterized with controllable pulse parameter transcranial magnetic stimulation

Pulse width dependence of motor threshold and input–output curve characterized with controllable pulse parameter transcranial magnetic stimulation

Persistent alterations in active and passive electrical membrane properties of regenerated nerve fibers of man and mice

Amyotrophic lateral sclerosis: Current perspectives from basic research to the clinic

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