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bioRxiv · 10.1101/2020.06.27.173054

Caudal-rostral progression of alpha motoneurone degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis

Kirby, A. J.·Mead, R.·Ichiyama, R. M.·Chakrabarty, S.
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Abstract

Mice with transgenic expression of human SOD1G93A 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 (-) and gamma ({gamma}-) MNs overlap in size. Therefore, using molecular markers and synaptic inputs, we quantified the survival of -MNs and {gamma}-MNs at the lumbar and cervical spinal segments of 3- and 4-month SOD1G93A 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 -MN degeneration with complete {gamma}-MN sparing. At 3-months the cervical spinal cord had more -MNs per ventral horn than the lumbar spinal cord, in SOD1G93A 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 -MN and CST of the lumbar spinal cord are more susceptible to degeneration in SOD1G93A mice. Hence, there is spatial and temporal caudal-rostral progression of -MN and CST degeneration in SOD1G93A mice. HighlightsO_LISOD1G93A mice display a caudal-rostral progression of motor impairment. C_LIO_LILumbar spinal cord of SOD1G93A mice has an enhanced susceptibility to degeneration. C_LIO_LISOD1G93A mice exhibit a caudal-rostral progression of -MN and CST degeneration C_LI

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Kirby, A. J., Mead, R., Ichiyama, R. M., Chakrabarty, S.. 2020-06-28. Caudal-rostral progression of alpha motoneurone degeneration in the SOD1G93A mouse model of amyotrophic lateral sclerosis. https://doi.org/10.1101/2020.06.27.173054

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