Development Of Experimental Encephalomyelitis Research Articles

Experimental Autoimmune Encephalomyelitis of Mice: IgGs from the Sera of Mice Hydrolyze miRNAs

It was shown that the spontaneous development of experimental encephalomyelitis (EAE) in C57BL/6 mice occurs due to changes in the profile of bone marrow stem cells differentiation. This leads to the appearance of lymphocytes producing antibodies-abzymes that hydrolyze DNA, myelin basic protein (MBP), and histones. The activity of abzymes in the hydrolysis of these auto-antigens slowly but constantly increases during the spontaneous development of EAE. Treatment of mice with myelin oligodendrocyte glycoprotein (MOG) leads to a sharp increase in the activity of these abzymes with their maximum at 20 days (acute phase) after immunization. In this work, we analyzed changes in the activity of IgG-abzymes hydrolyzing (pA)23, (pC)23, (pU)23, and six miRNAs (miR-9-5p, miR-219a-5p, miR-326, miR-155-5p, miR-21-3p, and miR-146a-3p) before and after mice immunization with MOG. Unlike abzymes hydrolyzing DNA, MBP, and histones, the spontaneous development of EAE leads not to an increase but to a permanent decrease of IgGs activity of hydrolysis of RNA-substrates. Treatment of mice with MOG resulted in a sharp but transient increase in the activity of antibodies by day 7 (onset of the disease), followed by a sharp decrease in activity 20-40 days after immunization. A significant difference in the production of abzymes against DNA, MBP, and histones before and after mice immunization with MOG with those against RNAs may be since the expression of many miRNAs decreased with age. This can lead to a decrease in the production of antibodies and abzymes that hydrolyze miRNAs with age mice.

Effect of Myelin Oligodendrocyte Glycoprotein (MOG35-55) on Cell Differentiation and Antibodies-Abzymes Production in Transgenic EAE-Prone Th Mice with T Cells Response during the Development of Experimental Encephalomyelitis

The mechanisms of multiple sclerosis development are still unknown. It was shown that the development of Experimental Autoimmune Encephalomyelitis (EAE) in EAE prone C57BL/6mice (model mimicking human multiple sclerosis) having B and T lymphocyte responses is associated with modification in the differentiation profiles of bone marrow Hematopoietic Stem Cells (HSCs) and the increase in lymphocyte proliferation. T cell responses characterize other EAE transgenic prone Th mice. Different characteristics of the autoimmune reaction in Th mice were analyzed. During the development of EAE (and inflammation processes), the differentiation profiles of Th mice bone marrow HSCs (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T and B lymphocytes) were noticeably or significantly different in male and female mice before and after their immunization with myelin oligodendrocyte glycoprotein (MOG35-55).The patterns of B and T (including CD4 and CD8 cells) lymphocytes proliferation in several organs (spleen, thymus, bone marrow, blood and lymph nodes) during spontaneous (completely untreated mice) and MOG-treatment-accelerated development of EAE was also remarkably or significantly different in male and female mice. All these changes in male and female mice, despite some differences, were coupled with the increase in the concentrations of autoantibodies against DNA, myelin basic protein, and MOG, and with the increase in the relative activity of catalytic antibodies hydrolyzing these antigens. A comparison of the changes in a large number of parameters characterizing the development of EAE in Th and C57BL/6 mice was carried out. It was shown that MOG very much accelerates the development of EAE in Th mice. Despite some differences, the general patterns of the developing of spontaneous and MOG-accelerated EAE in Th male and female mice and in C57BL/6 mice are similar to a notable extent.