Influence of interleukin-10 on factors of immune and antioxidant protection of the brain, thymic function and behaviour in the cuprizone mouse model of demyelination
Background. The role of macrophages, Tlymphocytes and factors of oxidative stress in damage to the nerve cells of the brain leading to disruption of their functioning is known. Thymic hormone thymulin exhibits immunomodulating properties whereas interleukin10 possesses pronounced antiinflammatory properties and affects neurogenesis. This work aimed to study changes in the content of macrophages, Tlymphocytes, malondialdehyde, activity of antioxidant enzymes in the brain, blood thymulin levels, and behavioral reactions in mice with cuprizone demyelination model treated with recombinant human IL10 (rhIL10). Materials and methods. Adult 129/Sv mice received cuprizone daily with food for 3 weeks. Starting from day 7 of cuprizone diet, rhIL10 was administered intraperitoneally at a dose of 5 µg/kg (total of 3 injections, with an interval of 3 days). Results. The number of latexphagocyting macrophages, CD3+ Tcells and malondialdehyde content increased while the activity of antioxidant enzymes decreased in the brain of cuprizonetreated mice. Following rhIL10 injections, we observed a decrease in the number of CD3+ Tcells and macrophage activity and an increase in the superoxide dismutase, catalase and glutathione peroxidase activities. Besides, the thymulin blood level increased. Interestingly, after cytokine injection we observed an increase in the horizontal locomotor, emotional and exploratory activities, being decreased by cuprizone. Conclusions. Locomotor, emotional and exploratory activity tests showed that rhIL10 improved the central nervous system functioning in the cuprizonetreated mice. RhIL10 effect in mice on cuprizone diet was mainly associated with changes in the number of brain Tlymphocytes, the activity of macrophages and antioxidant enzymes, as well as the endocrine function of the thymus. Interleukin10 or agents/approaches enhancing its synthesis in the central nervous system might be promising in the demyelinating pathology treatment schemes.
Full Text:PDF (Русский)
Abdurasulova I.N. The role of immune and glial cells in neurodegenerative processes. Med. akadem. zhurnal. 2011. Vol. 11. № 1. P. 1229.
Gonzalez H. Tcellmediated regulation of neuroinflammation involved in neurodegenerative diseases. J. Neuroinflammation. 2014. Vol. 11. № 201. 11 p. doi: 10.1186/s1297401402018.
Strle K. Interleukin10 in the brain. Crit. Rev. Immunol. 2001. Vol. 21. № 5. P. 427449. doi: 10.1615/CritRevImmunol.v21.i5.20.
Klose J. Suppression of experimental autoimmune encephalomyelitis by interleukin10 transduced neural stem/progenitor cells. J. Neuroinflamma-tion. 2013. Vol. 10. P. 117. doi: 10.1186/1742209410117.
Meng J. The Critical Role of IL10 in the Antineuroinflammatory and Antioxidative Effects of Rheum tanguticum on Activated Microglia. Oxida-tive medicine and cellular longevity. 2018. Vol. 6. P. 112. doi: 10.1155/2018/1083596.
Labunets I.F. Capacity of bone marrow granylocyte and macrophage precursors in mice of different strains for in vitro colony formation under changes thymuline level in the organism and cell cultures. Genes & Cells. 2017. Vol. 12. № 2. P. 97103. doi: 10.23868/201707021. [In Russian].
Csaba G. The immunoendocrine thymus as a pacemaker of lifespan. Acta Microbiol. Immunol. Hung. 2016. Vol. 63. № 2. Р. 139158. doi: 10.1556/030.63.2016.2.1.
PerezAsensio F.J. Interleukin10 regulates progenitor differentiation and modulates neurogenesis in adult brain. J. Cell. Sci. 2013. Vol. 126. P. 42084219. doi: 10.1242/jcs.127803.
Labunets I.F. Changes of thymic endocrine function, brain macrophages and Tlymphocytes in mice of different age after administration of neuro-toxin cuprizone and cytokine. International Neurogical Journal. 2018. № 4(98). Р. 155161. doi: 10.22141/222407184.108.40.2068.139434. [In Russian].
Kang Z. IL17induced Act1mediated signaling is critical for cuprizoneinduced demyelination. J. Neurosci. 2012. Vol. 32. № 4. P. 82848292. doi: 10.1523/JNEUROSCI.084112.2012.
Labunets I.F. CuprizoneInduced Disorders of Central Nervous System Neurons, Behavioral Reactions, Brain Activity of Macrophages and Anti-oxidant Enzymes in the Mice of Different Ages: Role of Leukemia Inhibitory Factor in their Improvement. J. Aging Geriatr. Med. 2017. Vol. 1. № 2. 8 p. doi: 10.4172/AGM.1000104.
Praet J. Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis. J. Neubiorev. 2014. Vol. 47. P. 485505. doi.org/10.1016/j.neubiorev.2014.10.004.
Labunets І.F., Mel'nik N.O., Rodnіchenko A.Є. ta іn. Influence of recombinant human interleukin10 on structure of central nervous system neurons and behavioral reactions in mice with cuprizone model of multiple sclerosis. Conference abstracts. Innovative trends in genetic and regenerative medicine (November 910, 2017, Кyiv, Ukraine). Klіtinna ta organna transplantologіja Dodatok 2017. Vol. 5. № 2. P. 240241.
Labunets I.F. Possibilities and prospects of the application of the in vivo and in vitro toxic cuprizone model for demyelination in experimental and clinical neurology (literature review and own research results). Ukrai'ns'kiy nevrologichniy zhurnal. Ukrainian Neurological Journal. 2018. № 2. P. 6368. ISSN 19984235 (print), ISSN 25221183 (online); doi: https://doi.org/10.30978/UNZ2018263.
Walker J.M. The Protein Protocols Handbook. Totowa, New Jersey: Humana Press Inc. 2002. 1139 p.
Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem. 1978. Vol. 86. № 1. P. 271278.
Labunets I.F. Thymic hormones, antioxidant enzymes and neurogenesis of bulbus olfactorius in rats with parkinsonism: the effect of melatonin. Int. J. Phys. Pathophys. 2016. Vol. 7. № 4. P. 285298.
Amikishieva A.V. Behavioral phenothyping: upto date methods and equipment. Vestnik VOGiS. 2009. Vol.13. № 3. P. 529542.
Guillemin G.J., Brew B.J. Microglial, macrophages, perivascular macrophages, and pericytes: a review of function and identification. Brew. Biol. 2004. Vol. 75. P. 288239. doi: 10.1189/jlb.03.03114.
Ozenci V. Multiple sclerosis:levels of interleukin10secreting blood mononuclear cells are low in untreated patients but augmented during inter-feronbeta1b treatment. Scand. J. Immunol. 1999. Vol. 49. № 5. P. 55461. PMID: 10320650.
Pichkur L.D. Influence of transplantation of mesenchymal stem cells and interleukin10 on experimental allergic encephalomyelitis course. Ukrai'ns'kyj nevrologichnyj zhurnal. 2018. № 1. P. 5663.
Gudi V. Glial response during cuprizoninduced de and remyelination in the CNS: lessons learned. Front. Cell. Neurosci. 2014. 8 (Article 73). 24 p. doi: 10.3389/fncel.2014.00073.
Haddad J.J. The antiinflammatory and immunomodulatory activity of thymulin peptide is NFkB dependent and involves the downregulation of I kBα. Am. J. Med. Biol. Res. 2013. Vol. 1. № 2. Р. 4149. doi: 10.12691/ajmbr122.
KoldricZivanovic N. Regulation of adrenal glucocorticoid synthesis by interleukin10: a preponderance of IL10 receptor in the adrenal zone fasciculate. Brain Behave Immun. 2006. Vol. 20. № 5. P. 460468. doi: 10.1016/j.bbi.2005.09.003
SerradeOliveira N. Behavioural changes observed in demyelination model shares similarities with white matter abnormalities in humans. Be-hav. Brain Res. 2015. Vol. 287. P. 265275. doi: 10.1016/j.bbr.2015.03.038.
Labunets I.F. The thymus and adaptive changes of the function of the immune system in aging: the role of pineal gland factors. Bukov. med. visnyk. 2009. Vol. 13. № 4. P. 186190.
Noorzehi G. Microglia polarization by methylprednizolone acetate accelerates cuprizone induced demyelination. J. Mol Histol. 2018. Vol. 49. № 5. P. 471479. doi: 10.1007/s107350189786z.
Latorre E. IL10 counteracts proinflammatory mediator evoked oxidative stress in Caco2 cells. Mediators of Inflammation. 2014. Vol. 2014. Ar-ticle ID 982639, 6 p. http://dx.doi.org/10.1155/2014/98.
Morreira A.P. Interleukin10 but not transforming growth factor beta inhibits murine activated macrophages Paracoccidioides brasiliensis killing: effect on H2О2 and NO production. Cellular Immunology. 2010. Vol. 263. № 2. P. 196203. doi: 10.1016/j.cellimm.2010.03.016.
Cymbaljuk V.І. Effects of human Wharton’s jellyderived mesenchymal stem cells and interleukin10 on behavioural responses of rats with exper-imental allergic encephalomyelitis. Klitynna ta organna transplantologija. 2015. Vol. 3. № 1. P. 4045.
Labunets I.F. Neuroprotective effect of the recombinant human leukemia inhibitory factor in mice with an ex-perimental cuprizone model of multiple sclerosis: possible mechanisms. Biopolymers and Cell. 2018. Vol. 34. № 5. P. 350360. doi: http://dx.doi:org/10.7124/bc.000989.
Copyright (c) 2019 INTERNATIONAL NEUROLOGICAL JOURNAL
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Publishing House Zaslavsky, 1997-2019