NMDA-receptors regulate the genes of key immune functions in lymphocytes of multiple sclerosis patients

• Kuzmina U.Sh.
• Zainullina L.F.
• Sadovnikov S.V.
• Vakhitov V.A.
• Bakhtiyarova K.Z.
• Vakhitova Yu.V.

Abstract

Multiple sclerosis is an autoimmune demyelinating inflammatory disorder ofthe central nervous system. In addition to autoimmune mechanisms neurotransmitter glutamate plays a significant role in the destruction of myelin, oligodendrocyte and neuronal death. It was shown that glutamate produced by activated macrophages and microglia by ionotropic and metabotropic receptors mediates excitotoxic process which contributes to the formation and maintenance of neurodegeneration in MS. Recently the evidences were found that glutamate may act as an immunomodulator by control of functions of infiltrated T-cells in inflammation tissues. Furthermore, immunomodulation may be carried out by the glutamate ionotropic receptors, in particular the NMDA-subtype, at the level of peripheral T-lymphocytes. The aim of this study was the investigation of the role of NMDA-receptors in the regulation of immunocompetent cells functions by the comparative analysis of the genes expression profile in peripheral blood mononuclear cells from multiple sclerosis patients using a commercial kit Human Signal Transduction Pathway Finder PCR Array. It has been shown that in peripheral blood mononuclear cells from multiple sclerosis patients the antagonist NMDA-receptors (+)-МК801 caused the alteration of expression of genes which are composed to the closely related and overlapping clusters of biological processes such as apoptosis, phosphorylation, cytokine and chemokine signaling. These data suggest that the NMDA-receptors could be involved in the modulation of some of the key functions of mononuclear cells, as well as in the regulation of chemotaxis of immune cells in patients with multiple sclerosis.

Keywords:multiple sclerosis; NMDA-receptors; transcriptome analysis; peripheral blood mononuclear cells

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