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Contents of Myelin Basic Protein and Autoantibodies against Brain Proteins in the Experimental Antiphospholipid Syndrome

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Neurophysiology Aims and scope

We examined the content of autoantibodies against brain proteins, content of myelin basic protein (MBP), and level of NO synthesis in the cerebellum and cerebral hemispheres on day 18 of pregnancy in BALB/c mice with the experimental antiphospholipid syndrome (APS); the effects of L-arginine on the above indices were also evaluated. As was found, the contents of autoantibodies against brain proteins having the molecular masses 120, 150, and > 170 kDa were greater than in the control. Under APS conditions, the amount of eNOS-produced NO was relatively insufficient; this was observed against the background of total hyperproduction of NO synthesized by iNOS in blood serum. In APS mice, the contents of stable NO metabolites, NO2 and NO3, in the cerebellum were higher, while these levels in the cerebral hemispheres were lower with respect to the control. There were reasons to believe that the effects of L-arginine under APS conditions of and cerebral dysfunction are provided not only at the expense of influences upon the NO system, but also via antioxidant and cytoprotective properties of this amino acid. In pregnant APS mice, the content of MBP (95–110 kDa) in the cerebellum and that of MBP (18.4 kDa) in the cerebral hemispheres were greater than in the control. In APS animals, administration of L-arginine provided increase in the content of MBP (18.4 kDa) in the cerebral hemispheres compared with the respective index with no treatment. Our results show that the remyelination processes in animals with the APS are activated; this may be interpreted as a compensatory response to the injury.

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References

  1. T. Fleetwood, R. Cantello, and C. Comi, “Antiphospholipid syndrome and the neurologist: from pathogenesis to therapy,” Front. Neurol., 9, 1001 doi:https://doi.org/10.3389/fneur.2018.01001 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  2. L. A. Kalashnikova, “Cerebrovascular disorders in antiphospholipid syndrome,” Ann. Klin. Eksper. Nevrolog., 5, No. 1, 39–43 (2011).

    Google Scholar 

  3. N. Costedoat-Chalumeau, G. Guettrot-Imbert, and V. Leguern, “Pregnancy and antiphospholipid syndrome,” Rev. Med. Interne., 33, No. 4, 209–216 (2012).

    Article  CAS  PubMed  Google Scholar 

  4. E. L. Nasonov, Antiphospholipid Syndrome, Litterra, Moscow (2004).

    Google Scholar 

  5. A. B. Poletayev and F. Aliyeva, “Autoantibodies and the immunopathology of pregnancy,” Prakt. Med., No. 43, 20–24 (2010).

    Google Scholar 

  6. V. A. Sobolyev, V. A. Proshyn, S. G. Morozov, et al., “State of health of children born by mothers with different contents of antibodies against a few nerve tissue proteins and protein fractions,” Pediatriya, 5, 44–50 (2004).

    Google Scholar 

  7. I. F. Ricarte, L. A. Dutra, F. F. Abrantes, et al., “Neurologic manifestations of antiphospholipid syndrome,” Lupus, 27, No. 9, 1404–1414, https://doi.org/10.1177/0961203318776110(2018).

  8. J. Graf, “Central nervous system manifestations of antiphospholipid syndrome,” Rheum. Dis. Clin. North. Am., 43, No. 4, 547–560 (2017).

    Article  PubMed  Google Scholar 

  9. T. G. D’Aversa, E. A. Eugenin, L. Lopez, et al., “Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: implications for the pathogenesis of multiple sclerosis,” Neuropathol. Appl. Neurobiol., 39, No. 3, 270–283 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  10. A. V. Astakhin, O. O. Yevlasheva, and B. N. Levitan, “Clinical and diagnostic importance of the myelin basic protein and neurospecific enolase in medical practice,” Astrakhan. Med. J., 4, No. 11, 9–17 (2016).

    Google Scholar 

  11. P. R. J. Ames, J. R. Batuca, A. Ciampa, et al., “Clinical relevance of nitric oxide metabolites and nitrative stress in thrombotic primary antiphospholipid syndrome,” J. Rheumatol., 37, No. 12, 2523–2530 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. V. P. Reutov, E. G. Sorokina, N. V. Samosudova, et al., “Geodynamics of the brain: Glutamatergic system and nitric oxide cycle in the regulation of cerebral circulation. A novel concept,” Pacific Med. J., 3, 37–45 (2017).

    Google Scholar 

  13. Yu. M. Stepanov, I. N. Kononov, A. I. Zhurbina, et al., “Arginine in medical practice (a review),” Zh. AMS Ukraine, 10, No. 1, 340–352 (2004).

    Google Scholar 

  14. G. V. Zaichenko, Yu. B. Lar’yanovs’ka, and T. V. Deyeva, “Morphological state of the womb and placenta in expetimental modeling of the gestation antiphospholipid syndrome in mice,” Ukr. Med. Almanakh, 14, No. 4, 136–141 (2011).

    Google Scholar 

  15. О. H. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, “Protein measurement with the Folin phenol reagent,” J. Biol. Chem., 193, No. 1, 265–275 (1951).

    CAS  PubMed  Google Scholar 

  16. U. K. Laemmli, “Cleavage of structural proteins during the assembly of the head of bacteriophage T4,” Nature, 227, No. 5259, 680–685 (1970).

    Article  CAS  PubMed  Google Scholar 

  17. H. Towbin, T. Staehelin, and J. Gordon, “Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications”, Proc. Natl. Acad. Sci. USA, 76, No. 9, 4350–4354 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. L. C. Green, D. A. Wagner, J. Glogowski, et al., “Analysis of nitrate, nitrite and [15N] nitrate in biological fluids,” Analyt. Biochem., 126, No. 1, 131–138 (1982).

    Article  CAS  PubMed  Google Scholar 

  19. I. O. Kiselyk, M. D. Lutsyk, and L. Yu. Shevchenko, “Peculiarities of estimation of the nitrate and nitrite amounts in blood of the patients with virus hepatitis and jaundices related to other pathologies,” Lab. Diagnostics, 3, 43–45 (2001).

    Google Scholar 

  20. A. B. Poletaev and S. G. Morozov, “Changes of maternal serum natural antibodies of IgG class to proteins МBP, S100, ACBP14/18 and MP65 and embryonicmisdevelopments in humans,” Human Antibody, 9, No. 4, 216–222 (2000).

    Google Scholar 

  21. V. A. Aleinik, S. M. Babich, Kh. N. Negmatasheva, et al., “Peculiarities of the immunological shifts in women with miscarriage and the presence of autoantibodies,” Molod. Uchen., No. 22, 411–413 (2017).

    Google Scholar 

  22. N. Bizzaro, “Autoantibodies as predictor of disease: the clinical and experimental evidence”, Autoimmun. Rev., 6, No. 6, 325–333 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. J. D. Alves, L. J. Mason, P. R. J. Ames, et al., “Antiphospholipid antibodies are associated with enhanced oxidative stress, decreased plasma nitric oxide and paraoxonase activity in an experimental mouse model,” Rheumatology (Oxford), 44, No. 10, 1238–1244 (2005).

    Article  Google Scholar 

  24. S. Ramesh, C. N. Morrell, C. Tarango, et al., “Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2,” J. Clin. Invest., 121, No. 1, 120–131 (2011).

    Article  CAS  PubMed  Google Scholar 

  25. C. Mineo, “Inhibition of nitric oxide and antiphospholipid antibody-mediated thrombosis,” Curr. Rheumatol. Rep., 15, No. 5, 324 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  26. E. Svenungsson, M. Andersson, L. Brundin, et al., “Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus,” Ann. Rheum. Dis., 60, No. 4, 372–379 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. V. O. Kurovs’ka, V. P. Pishak, and S. S. Tkachuk, “Role of nitric oxide in ischemic and ischemico-reperfusional damages of the brain,” Bukovin. Med. Visn., 12, No. 4, 143–149 (2008).

    Google Scholar 

  28. Ch. López-Pedrera, N. Barbarroja, Y. Jimenez-Gomez, et al., “Oxidative stress in the pathogenesis of atherothrombosis associated with antiphospholipid syndrome and systemic lupus erythematosus: new therapeutic approaches,” Rheumatology (Oxford), 55, No. 12, 2096–2108 (2016).

    Article  Google Scholar 

  29. P. Patrikios, C. Stadelmann, A. Kutzelnigg, et al., “Remyelination is extensive in a subset of multiple sclerosis patients”, Brain, 129, Pt. 12, 3165–3172 (2006).

  30. F. Ruffini, T. E. Kennedy, and J. P. Antel, “Inflammation and remyelination in the central nervous system: a tale of two systems,” Am. J. Pathol., 164, No. 5, 1519–1522 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  31. H.F. Kuipers, J. Yoon, J.van Horssen, et al., “Phosphorylation of αB-crystallin supports reactive astrogliosis in demyelination”, Proc. Natl. Acad. Sci. USA. 114, No. 9, 1745–1754 (2017).

    Article  Google Scholar 

  32. A. Fontana, W. Fierz, and H. Wekerle, “Astrocytes present myelin basic protein to encephalitogenic T-cell lines”, Nature, 307, No. 5948, 273–276 (1984).

    Article  CAS  PubMed  Google Scholar 

  33. H. Kıray, S. L. Lindsay, S. Hosseinzadeh, et al., “The multifaceted role of astrocytes in regulating myelination,” Exp. Neurol., 283, Pt. B, 541–549 (2016).

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Yaremchuk, O.Z. Contents of Myelin Basic Protein and Autoantibodies against Brain Proteins in the Experimental Antiphospholipid Syndrome. Neurophysiology 52, 116–123 (2020). https://doi.org/10.1007/s11062-020-09860-7

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