The pathologic underpinnings of upper and lower motor neuron deficits in ALS include neuronal loss and gliosis in large neurons of "canonical" regions, including motor cortex, lamina IX of the ventral horn of the spinal cord, and somatic motor cranial nerve nuclei of the brainstem (XII, IX, and V) [ 2].
Coexistent lumbar stenosis accounts for lower motor neuron deficits and may mask long tract signs due to compression in the L4-S2 (epiconus) region [ 6, 12].
All FTLD-TDP cases either presented with motor neuron disease or developed motor neuron deficits and were best fit neuropathologic criteria for FTLD-TDP type B with TDP-43 inclusions in spinal cord motor neurons and frontal and/or temporal cortex [ 24].
Motor neuron loss is characteristic of cervical spinal cord injury (SCI) and contributes to functional deficit.
Motor neuron population model.
Motor neuron pathology was absent.
These transgenic mice develop progressive motor neuron loss and neurological deficits and, although not perfectly predictive of human ALS, are useful to screen potential drugs for clinical trial.
Recently, the effect of ablating the 3 isoforms of C9ORF72 protein from neurons and glia has been examined, demonstrating a reduction in body weight but no motor neuron degeneration or motor deficits [ 15].
Moreover, the finding that downregulation of the zebrafish orthologue of C9orf72 leads to both altered morphology of motor neuron axons and locomotor deficits, and that these features are reversed upon overexpression of wild-type human C9orf72, further support the notion that C9orf72 loss of function is detrimental [ 14].
The majority of these mice recapitulate many characteristics of ALS, including progressive motor deficits, hindlimb paralysis, motor neuron degeneration and early death (6, 12, 13).
Motor deficits and abnormal motor neuron axons have been described following knockdown of C9orf72 in zebra-fish [ 2], although more recent studies in mice have found no effect of complete lack of C9ORF72 on motor function [ 15].
