Caudal-rostral progression of alpha motoneurone degeneration in the SOD1G93Amouse model of amyotrophic lateral sclerosis

Mice with transgenic expression of human SOD1 G93A are a widely used model of ALS, with a caudal-rostral progression of motor impairment. Previous studies have quantified the progression of motoneurone (MN) degeneration based on size, even though alpha (α-) and gamma (γ-) MNs overlap in size. Therefore, using molecular markers and synaptic inputs, we quantified the survival of α-MNs and γ-MNs at the lumbar and cervical spinal segments of 3- and 4-month SOD1 G93A mice, to investigate whether there is a caudal-rostral progression of MN death. By 3-months, in the cervical and lumbar spinal cord, there was α-MN degeneration with complete γ-MN sparing. At 3-months the cervical spinal cord had more α-MNs per ventral horn than the lumbar spinal cord, in SOD1 G93A mice. A similar spatial trend of degeneration was observed in the corticospinal tract, which remained intact in the cervical spinal cord at 3- and 4-months of age. These findings agree with the corticofugal synaptopathy model, that α-MN and CST of the lumbar spinal cord are more susceptible to degeneration in SOD1 G93A mice. Hence, there is spatial and temporal caudal-rostral progression of α-MN and CST degeneration in SOD1 G93A mice. Highlights SOD1 G93A mice display a caudal-rostral progression of motor impairment. Lumbar spinal cord of SOD1 G93A mice has an enhanced susceptibility to degeneration. SOD1 G93A mice exhibit a caudal-rostral progression of α-MN and CST degeneration