Long-term measurement of muscle denervation and locomotor behavior in individual wild-type and ALS model mice

Abstract

The increasing number of mouse models of human degenerative and injury-related diseases that affect motor behavior raises the importance of in vivo methodologies allowing measurement of physiological and behavioral changes over an extended period of time in individual animals. A method that provides long-term measurements of muscle denervation and its behavioral consequences in individual mice for several months is presented in this article. The method is applied to mSod1G93A mice, which model human amyotrophic lateral sclerosis (ALS). The denervation process of gastrocnemius and soleus muscles in mSod1G93A mice is demonstrated for up to 3 mo. The data suggest that as muscle denervation progresses, massive behavioral compensation occurs within the spinal cord that allows animals to walk almost normally until late ages. Only around the age of 84 days is the first sign of abnormal movement during walking behavior detected as an abnormal tibialis anterior activity profile that is manifested in subtle but abnormal swing movement during walking. Additionally, this method can be used with other mouse models of human diseases, such as spinal cord injury, intracerebral hemorrhage, Parkinson's diseases, and spinal muscular atrophy.