Abstract
Canine degenerative myelopathy (DM) is an adult-onset neurodegenerative disease considered a spontaneous model of human amyotrophic lateral sclerosis (ALS). Neuroinflammation occurs in both DM and ALS, and crosstalk between the central nervous system and systemic immunity has been demonstrated in ALS. To investigate this interaction in DM, we analyzed peripheral blood and spinal cord tissues using real-time RT-PCR and immunofluorescence. In peripheral blood, mRNA expression of interleukin (IL)-18 and nod-like receptor protein 3 was significantly increased compared with intervertebral disk herniation controls. IL-10 and caspase-1 were elevated, whereas tumor necrosis factor-α was decreased relative to healthy controls. C-C motif chemokine receptor 2 expression showed a moderate negative correlation with disease duration. Immunofluorescence revealed a few transmembrane protein 119(-) and mannose receptor C-type 1(+) cells, indicating limited infiltration of peripheral blood-derived macrophages into the spinal cord. Transcriptional analysis of spinal cords with different degrees of degeneration showed increased expression of activated astrocyte markers (serping1 and S100A10) and C-C motif chemokine ligand 2 in moderately to severely degenerated tissues. Furthermore, immunohistochemical analysis revealed increased CCL2 protein expression in the affected spinal cords. These findings suggest that systemic immune activation contributes to spinal neuroinflammation in DM, although its limited cellular infiltration implies a minor role in neurodegeneration.