Role of glial fibrillary acidic protein (GFAP) and neurofilament (NF) expression in the pathophysiology of canine distemper encephalomyelitis

Abstract

Objectives: Canine distemper virus (CDV), a member of the genus Morbillivirus of the family Paramyxoviridae, is the causative agent of canine distemper, a fatal and highly contagious disease that affects dogs and other carnivores. This study aimed to investigate whether there is a correlation between glial fibrillary acidic protein (GFAP) and neurofilament (NF) expression in canine distemper encephalomyelitis (CDE) and the severe neuropathology that occurs. Materials and Methods: GFAP and NF expression levels in the brain tissue of 13 dogs diagnosed with CDE were investigated by immunohistochemical method. Results: The results of the study revealed that GFAP (P < 0.005) and NF (P < 0.005) expression levels in brain tissue were significantly increased in CDV-infected dogs compared to healthy, uninfected dogs. GFAP expression was mainly observed in endothelial cells and astrocytes, whereas NF expression was mainly found in neurons. In addition, it was found that the expression of both GFAP and NF was more pronounced in the areas with the most severe neuropathological findings. Conclusions: This study demonstrated pathological astrocyte reactivation and neuronal degeneration at the molecular level. These findings provide information about the stage of the disease. This study clearly demonstrated that detailed information about the prognosis of the disease can be obtained from GFAP and NF expression. Since GFAP/NF levels provide information about the severity of the disease, they can be used clinically. Therefore, further research into the involvement of GFAP and NF expression in the pathophysiology of CDE has great potential to improve our understanding of this complex neurological disorder.

Keywords

• canine distemper
• GFAP
• NF
• neuropathology
• encephalomyelitis

References

1. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006; 7(1):41-53.
2. Al-Chalabi A, Miller CC. Neurofilaments and neurological disease. Bioessays. 2003; 25(4):346-355.
3. Barrett T. Morbillivirus infections, with special emphasis on morbilliviruses of carnivores. Vet Microbiol. 1999; 69(1-2):3-13.
4. Barrya DM, Millecamps S, Julien JP, Garciaa ML. New movements in neurofilament transport, turnover and disease. Exp Cell Res. 2007; 313(10):2110-2120.
5. Beineke A, Baumgärtner W, Wohlsein P. Cross-species transmission of canine distemper virus-an update. One Health. 2015; 13(1):49-59.
6. Beineke A, Puff C, Seehusen F, Baumgärtner W. Pathogenesis and immunopathology of systemic and nervous canine distemper. Vet Immunol Immunopathol. 2009; 127(1-2):1-18.
7. Dalldorf G, Douglass M, Robinson HE. Canine Distemper in The Rhesus Monkey (Macaca Mulatta). J Exp Med. 1938; 67(2):323-332.
8. De Zeeuw CI, Hoogland TM. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function. Front Cell Neurosci. 2015; 9:246.

9. Dincel GC, Atmaca HT. Nitric oxide production increases during Toxoplasma gondii encephalitis in mice. Exp Parasitol. 2015; 156:104-112.
10. Dincel GC, Kul O. eNOS and iNOS trigger apoptosis in the brains of sheep and goats naturally infected with the border disease virus. Histol Histopathol. 2015; 30(10):1233-1242.
11. Dincel GC, Kul O. Increased expressions of ADAMTS-13, neuronal nitric oxide synthase, and neurofilament correlate with severity of neuropathology in Border disease virus-infected small ruminants. PLoS One. 2015; 10(3):e0120005.
12. Dincel GC, Kul O. First description of enhanced expression of transforming growth factor-alpha (TGF-α) and glia maturation factor-beta (GMF-β) correlate with severity of neuropathology in border disease virus-infected small ruminants. Microb Pathog. 2019; 128:301-310.
13. Dincel GC, Yıldırım S. Overexpression of ADAMTS-13 and neuronal nitric oxide synthase relates with neuropathology in streptozotocin-induced type 1 diabetic rats. Int J Clin Exp Pathol. 2016; 9(4):4761-4778.
14. Dincel GC. First description of enhanced expression of glia maturation factor-beta in experimental toxoplasmic encephalitis. J Int Med Res. 2017; 45(6):1670-1679.
15. Hol EM, Pekny M. Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Curr Opin Cell Biol. 2015; 32:121-130.
16. Julien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol. 1998; 61:1-23.
17. Laping NJ, Teter B, Nichols NR, Rozovsky I, Finch CE. Glial fibrillary acidic protein: regulation by hormones, cytokines, and growth factors. Brain Pathol. 1994; 4(3):259-275.
18. Liu Q, Xie F, Alvarado-Diaz A, et al. Neurofilamentopathy in neurodegenerative diseases. Open Neurol. J. 2011; 5:58-62.
19. Liu Q, Xie F, Siedlak SL, et al. Neurofilament proteins in neurodegenerative diseases. Cell Mol Life Sci. 2004; 61(24):3057-3075.
20. Martinez-Gutierrez M, Ruiz-Saenz J. Diversity of susceptible hosts in canine distemper virus infection: a systematic review and data synthesis. BMC Vet Res. 2016; 12:12-78.
21. Mongin AA, Kimelberg HK. Functions of neuroglial cells. In: Kettenmann H, Ransom BR, eds. Neuroglia. 2nd ed.. , New York: Oxford University Press; 2005. p.550.
22. Murphy FA, Fauquet CM, Bishop DH, et al. Virus taxonomy: classification and nomenclature of viruses. London, UK: Elsevier Academic Press; 2012. p.672-684.
23. Mutinelli F, Vandevelde M, Griot C, Richard A. Astrocytic infection in canine distemper virus-induced demyelination. Acta Neuropathol. 1989; 77(3):333-335.
24. Norgren N, Rosengren L. Elevated neurofilament levels in neurological diseases. Brain Res. 2003; 987(1):25-31.
25. Perea G, Navarrete M, Araque A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 2009; 32:421-431.
26. Qiu W, Zheng Y, Zhang S, et al. Canine distemper outbreak in rhesus monkeys, China. Emerg Infect Dis. 2011; 17(8):1541-1543.
27. Sofroniew MV. Astrogliosis. Cold Spring Harb Perspect Biol. 2014; 7(2):a020420.
28. Summers BA, Appel MJ. Aspects of canine distemper virus and measles virus encephalomyelitis. Neuropathol Appl Neurobiol. 1994; 20(6):525-534.
29. Summers BA, Appel MJ. Demyelination in canine distemper encephalomyelitis: an ultrastructural analysis. J Neurocytol. 1987; 16(6):871-881.
30. Summers BA, Greisen HA, Appel MJ. Canine distemper and experimental allergic encephalomyelitis in the dog: comparative patterns of demyelination. J Comp Pathol. 1984; 94(4):575-589.
31. Vandevelde M, Kristensen F, Kristensen B, Steck AJ, Kihm U. Immunological and pathological findings in demyelinating encephalitis associated with canine distemper virus infection. Acta Neuropathol. 1982; 56(1):1-8.
32. Yuan A, Rao MV, Veeranna, Nixon RA. Neurofilaments at a glance. J Cell Sci. 2012; 125:3257-3263.