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.
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Data availability
All data generated for this study are available upon request from the corresponding author.
Abbreviations
- ALS:
-
amyotrophic lateral sclerosis
- Arg1:
-
Arginase-1
- BDNF:
-
Brain-derived neurotrophic factor
- CCL2:
-
CC motif chemokine ligand 2
- CCR2:
-
C-C motif chemokine receptor 2
- DM:
-
degenerative myelopathy
- IL:
-
interleukin
- iNOS:
-
inducible nitric acid synthase
- MRC1:
-
mannose receptor C-type 1
- NGF:
-
Nerve growth factor
- NLRP3:
-
nod-like receptor protein 3
- TMEM119:
-
transmembrane protein 119
- TNFα:
-
tumor necrosis factorα
- RI:
-
reference interval
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Acknowledgements
The authors would like to acknowledge Kazuhiro Watanabe and Shingo Miyawaki for sharing the experimental equipment, as well as Yuuta Nozue and Haruka Iseri for cooperation in sample collection.
Funding
This work was supported by an intramural research fund (President discretionary expenses) from Gifu university and JSPS KAKENHI Grant Number 19K15978.
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Shunya, Yui, Naohito and Satoshi designed the study. Shunya, Yui, Hiroaki, Kohei and Junya collected the experimental samples and the clinical data. Yui and Kei provided technical assistance. Osamu and Shinichiro conducted genetic test. Hiroki and Jun made diagnosis of DM by histopathological examination. Shunya collected and analyzed the experimental data and wrote the original draft of manuscript. All authors provided editorial input during manuscript editing.
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Yokota, S., Kobatake, Y., Yoshida, K. et al. Analysis of immune-related alterations in blood and spinal cord of canine degenerative myelopathy, a spontaneous model of amyotrophic lateral sclerosis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43838-5
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DOI: https://doi.org/10.1038/s41598-026-43838-5
