| Autor: |
Kirby AJ; School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK., Palmer T; School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK., Mead RJ; Sheffield Institute of Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK., Ichiyama RM; School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK., Chakrabarty S; School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK. |
| Abstrakt: |
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 motoneuron (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-MNs and CST of the lumbar spinal cord are more susceptible to degeneration in SOD1 G93A mice. Hence, there is a spatial and temporal caudal-rostral progression of α-MN and CST degeneration in SOD1 G93A mice. |
