We are now able to offer longitudinal, repeated in vivo electromyographic measurements in rodent models with motor impairment. These analyses provide sensitive longitudinal readouts about your drug candidates that are unaffected by the environmental or emotional status of your animals. Typical readouts are the Compound Muscle Action Potential (CMAP), Motor Unit Action Potential (MUAP) and Motor Unit Number Estimation (MUNE).
Longitudinal evaluation of the maximal CMAP amplitude in SOD1-G93A mice on a C57BL/6J background (SOD1-B6) as model of amyotrophic lateral sclerosis resulted in progressively decreasing levels, while amplitudes of non-transgenic (ntg) animals did not change with time. CMAP amplitudes of SOD1-B6 mice were at all time points significantly reduced compared to ntg mice (Fig.1A). Evaluation of the CMAP latency to peak resulted in progressively increasing values in SOD1-B6 mice. Differences between SOD1-B6 mice and ntg littermates were significant starting at week 14 (Fig.1B).
Figure 1: Longitudinal CMAP measurement in anesthetized SOD1-B6 mice. Longitudinal measurement of the CMAP amplitude in mV (A) and longitudinal CMAP latency to peak in ms (B) in 8-, 14-, and 20-week-old SOD1-B6 mice and ntg littermates. Two-way ANOVA followed by Bonferroni’s multiple comparisons post hoc test; mean ± SEM; n = 16 per group; mixed sex; **p<0.01, ***p<0.001. ntg, non-transgenic.
Repeated stimulation to test neuromuscular junctions’ fatigue-effects resulted in significantly reduced amplitudes in SOD1-B6 mice compared to ntg littermates at all time points. Differences did not significantly change with time (Fig.2A). Longitudinal evaluation of the motor unit action potential (MUAP) in SOD1-B6 mice resulted in significantly reduced amplitudes in SOD1-B6 compared to ntg littermates at all time points. Differences did not change with time (Fig.2B).
Figure 2: Longitudinal amplitude changes after repeated (rep.) stimulation and MUAP and measurement in anesthetized SOD1-B6 mice. Amplitude changes in percent after repeated stimulation (A) and longitudinal measurement of the MUAP amplitude in mV (B) in 8-, 14-, and 20-week-old SOD1-B6 mice and ntg littermates. Two-way ANOVA followed by Bonferroni’s multiple comparisons post hoc test; mean ± SEM; n = 16 per group; mixed sex; *p<0.05, ***p<0.001. ntg, non-transgenic.
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