Item

Abstract

Objectives: In the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), a selective degeneration of fast-fatigable motor units and consequently an early decline of contractile force in individual fast-twitch muscles have been observed in the preclinical stage. However, most human muscles include fast and slow motor units. Gastrocnemius-soleus group (GS) contains such a mixture of units. Methods: We have investigated changes in the mechanical properties of GS at different SOD1G93A stages in mice. For this purpose, the tibial nerve was repetitively stimulated with rectangular pulses and the force of GS twitches was recorded using a strain gauge fixed to the Achilles tendon. Results: Isometric and tetanic force were attenuated but not before the first clinical signs developed. However, already at preclinical stages, single twitches showed a slower decay compared to control. Consequently, fusion of GS twitches occurred at lower stimulus rates. Furthermore, already preclinically, the temporal course of successive twitch amplitudes changed during repetitive stimulation at increasing rates. The peak amplitudes as well as the potentiation following decay (fatigue) were lower in preclinical mice than in control. Discussion: The time-lapse analysis of the contractile pattern as well as of the twitch configuration of the mixed muscle GS have revealed distinctive differences between wild-type controls and preclinical SOD1G93A mice. It would be of interest to know whether these preclinical changes are also detectable in ALS patients.