Amyotrophic lateral sclerosis - evidence of early denervation of fast-twitch muscles

In the SOD transgenic ALS mouse model, motoneuron death has not been reported earlier than 90 days of age, the so-called pre-symptomatic phase. We recorded contractile force from the fast-twitch medial gastrocnemius and slow-twitch soleus muscles and their constituent motor units to determine the number of intact motor units during the asymptomatic phase of disease. We found an early, selective and progressive loss of the largest and fastest motor units in the MG muscle. No such loss was evident in the slowtwitch soleus muscle. This data indicates selective axon die-back of the motoneurons that innervate the largest and fastest motor units. This die-back occurs prior to the death of the motoneurons in the spinal cord. Evidence of fiber-type conversions to more fatigueresistant motor units suggested that this early loss may be slowed by increasing neuromuscular activity.