[The role of dopamine receptors in the modulation of mononuclear phagocytes in multiple sclerosis]. / Rol' retseptorov dofamina v modulyatsii mononuklearnykh fagotsitov pri rasseyannom skleroze.

OBJECTIVE: To investigate the role of dopamine receptor D1DR and D2DR in the production of cytokines interleukin-6 (IL-6) and IL-1ß by monocytes and macrophages in patients with relapsing-remitting multiple sclerosis (MS). MATERIAL AND METHODS: Ten patients with relapsing-remitting MS and 10 healthy subjects were examined. The level of IL-6 and IL-1ß production was assessed in culture supernatants obtained from CD14+ monocytes or macrophages stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). To study the role of dopamine receptors in the regulation of CD14+ monocytes or macrophages, samples of cells were incubated in the presence of specific D1DR or D2DR antagonists, after which IFN-γ/LPS were added to the cultures. Levels of cytokines in culture supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: The production of IL-6 and IL-1ß by CD14+ monocytes and macrophages was comparable between the groups. Blockade of D1DR suppressed cytokine production by CD14+ monocytes and macrophages in both groups. In contrast, blockade of D2DR increased the production of cytokines by CD14+ monocytes and did not affect cytokine production by macrophages in both groups. CONCLUSIONS: Targeting of dopaminergic receptors could be considered as an additional mechanism of immunomodulation in MS with both pro- and anti-inflammatory effects on cells of the innate immune system.

[A case of COVID-associated encephalopathy in a patient with multiple sclerosis]. / Klinicheskii sluchai COVID-assotsiirovannoi entsefalopatii u patsienta s rasseyannym sklerozom.

A case of acute encephalopathy manifested with impaired consciousness, hemichorrhea, speech and cognitive impairment in a female patient with COVID-19 and multiple sclerosis is presented. In the literature, there are isolated reports of such a combination of diseases, and therefore difficulties arise in carrying out differential diagnosis and prescribing therapy. Given the limited knowledge about the long-term consequences of COVID-19, systematic analysis of such cases and follow-up of such patients is necessary.

[A clinical case of multiple sclerosis with an episode of schizophrenia-like syndrome]. / Rasseyannyi skleroz s epizodom shizofrenopodobnogo sindroma.

The article presents a clinical observation of a schizophrenia-like disorder in a patient with multiple sclerosis (MS). The patient had highly active MS with a relapsing course, the diagnosis was made based on the McDonald 2017 criteria. During the course of a demyelinating disease of the nervous system, the patient developed an episode of psychotic disorders with symptoms of mutism, hallucinations, delusions and impaired thinking, which was quickly stopped in stationary conditions. This case is of particular interest to neurologists and psychiatrists, since psychotic disorders occur in MS patients and cause difficulties in diagnosis and treatment.

Effect of Fabomotizole on Brain Gene Expression in MR Rats in the Open Field Test.

Selective anxiolytic fabomotizole (Afobazol®) has affinity for the Sigma-1 chaperone receptor site, quinone reductase 2 (NQO2) and MAO-A regulatory sites, and melatonin receptor type 1 (MT1 receptor). The analysis of the effect of fabomotizole on the gene expression profile in the brain of MR (Maudsley Reactive) rats was carried out when modeling emotional stress in the open field test. A change in the expression of 14 genes was found, the results of the functional annotation of which showed that the mechanisms of action of fabomotizole may be associated with the regulation of translation of proteins (Rpl5, Rpl15, Ncl, and Ybx1), synaptic functions (Cplx2, Dlg4, Syngap1, Add1, Rab8b, Klc1, and Chn1), and cellular metabolism (Akr1d1, Bcat1, and Pkm).

[The role of glutamate in the pathogenesis of multiple sclerosis]. / Rol' glutamata v patogeneze rasseiannogo skleroza.

The results of recent studies indicate that the hyperactivation of the glutamatergic system plays an important role in the pathophysiology of multiple sclerosis (MS). In addition to the well-known direct toxic effect of the excessive extracellular level of the glutamate neurotransmitter on neurons, additional mechanisms of glutamate-induced cell damage have been described in the literature, including effects on oligodendrocytes, astrocytes, endothelial cells and immune cells. The study of these toxic effects will reveal the possible link between various pathological hallmarks of MS, such as axonal damage, oligodendrocyte death, demyelination, neurodegeneration, autoimmune reactions and dysfunction of blood-brain barrier. Understanding the mechanisms underlying the glutamate toxicity will contribute to the development of new therapeutic approaches for the diagnosis and treatment of patients with MS. This review focuses on the mechanisms that lead to an increase in the concentration of neurotransmitter glutamate and excitotoxicity in the context of the pathogenesis of this disease. Also the authors present the data on existing and currently developed medicines and therapeutic approaches to regulate the activity of the glutamatergic system.

NMDA Receptors Regulate Genes Responsible for Major Immune Functions of Mononuclears in Human Peripheral Blood.

To determine the role of NMDA receptors in the functional regulation of immunocompetent cells, comparative assay was carried out for genes expressed in the mononuclears in peripheral blood of healthy persons under normal conditions and after blockade of these receptors. The genes, whose expression changed in response to blockade of NMDA receptors in mononuclears, encode the products involved in regulation of the major functions of immune cells, such as proliferation (IL4, VCAM1, and CDKN2A), apoptosis (BAX, MYC, CDKN2A, HSPB1, and CADD45A), activation (IL4R, IL4, VCAM1, and CDKN2A), and differentiation (IL4, VCAM1, and BAX).