IMMUNOLOGICAL CELULLAR-MOLECULAR MARKERS OF THE PERIPHERAL BLOOD OF А53Т MICE WITH GENETIC PREDISPOSITION TO PARKINSON’S DISEASE

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Abstract


The present experimental study aimed to find the most informative peripheral cellular-molecular immune markers, which can determine a risk of the development of Parkinson’s disease. The experiments were performed in transgenic mice of the A53T strain (2 months) characterized by an increased expression of alpha synuclein and genetically predisposed to Parkinson’s disease during aging. In comparison with the WT strain mice (control), A53T mice were found to have a reduced emotionality (increased horizontal motor activity and a significant decrease in defecation acts in the open field test) along with unchanged coordination and balance, tested using the Rotarod + hardware-software complex. These mice were also characterized by significant changes in the content of immune cell subpopulations in the peripheral blood - an increase in the percentage of CD3+T cells and CD3+4+T helper cells, a decrease in the content of CD19+B cells, with unaltered numbers of CD3+4+25+ 27-regulatory, CD19+25+B-regulatory cells and CD11b+115+monocytes. The percentage of T-regulatory cells expressing Toll-like receptors of the 2nd and 4th types (TLR2 and TLR4) was higher in A53T mice than in controls, while the number of cells expressing only TLR4 was reduced. The TLR2 expression did not differ between A53T and control mice. Analysis of the TLR2 and TLR4 expression on CD11b+115+monocytes has shown that the percentage of these cells with TLR4 was reduced in A53T mice compared to the control, while the content of cells with both TLR types did not depend on genotype. Proinflammatory cytokines (IL-6) prevailed over antiinflammatory (IL-10) in the supernatant of mononuclear blood cells of A53T mice suggesting the development of neuroinflammation.The study was supported by Russian Foundation of Basic Research (grant N18-015-00226 А).

Full Text

The present experimental study aimed to find the most informative peripheral cellular-molecular immune markers, which can determine a risk of the development of Parkinson’s disease. The experiments were performed in transgenic mice of the A53T strain (2 months) characterized by an increased expression of alpha synuclein and genetically predisposed to Parkinson’s disease during aging. In comparison with the WT strain mice (control), A53T mice were found to have a reduced emotionality (increased horizontal motor activity and a significant decrease in defecation acts in the open field test) along with unchanged coordination and balance, tested using the Rotarod + hardware-software complex. These mice were also characterized by significant changes in the content of immune cell subpopulations in the peripheral blood - an increase in the percentage of CD3+T cells and CD3+4+T helper cells, a decrease in the content of CD19+B cells, with unaltered numbers of CD3+4+25+ 27-regulatory, CD19+25+B-regulatory cells and CD11b+115+monocytes. The percentage of T-regulatory cells expressing Toll-like receptors of the 2nd and 4th types (TLR2 and TLR4) was higher in A53T mice than in controls, while the number of cells expressing only TLR4 was reduced. The TLR2 expression did not differ between A53T and control mice. Analysis of the TLR2 and TLR4 expression on CD11b+115+monocytes has shown that the percentage of these cells with TLR4 was reduced in A53T mice compared to the control, while the content of cells with both TLR types did not depend on genotype. Proinflammatory cytokines (IL-6) prevailed over antiinflammatory (IL-10) in the supernatant of mononuclear blood cells of A53T mice suggesting the development of neuroinflammation. The study was supported by Russian Foundation of Basic Research (grant N18-015-00226 А). Keywords: болезнь Паркинсона; трансгенные мыши линии А53Т; субпопуляции иммунных клеток; Толл-подобные рецепторы 2 и 4 типов; про- противовоспалительные цитокины.

About the authors

G Idova

Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk


E Alperina

Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk


S Zhanaeva

Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk


M Gevorgyan

Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk


M Tihonova

Scientific Research Institute of Physiology and Basic Medicine, Novosibirsk


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Copyright (c) 2019 Idova G., Alperina E., Zhanaeva S., Gevorgyan M., Tihonova M.

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