Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

We analyzed cultures of 5 independent myoblast lines from human skeletal muscles. It was shown that the content of desmin-positive cells in cultures at early passages exceeds 90%. Typical morphofunctional signs of myogenic differentiation disturbances were identified and their dynamics was studied. Signs of alternative adipogenic and chondrogenic differentiation of cells were revealed. Based on these data, limitations for the use of myoblast cultures of certain passages for biomedical research and cell therapy were evaluated.

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Центральный понтинный миелинолиз (ЦПМ) -это острая ограниченная симметричная невоспалительная демиелинизация в области средней части основания моста мозга. У 10% пациентов с ЦПМ демиелинизация возникает и за пределами моста: средний мозг, таламус, базальные ган-глии и мозжечок [1]. ЦПМ впервые был описан в 1959 г. R.D. Adams и соавт. в докладе о четырех пациентах с псевдобульбарным синдромом и тетраплегией [2]. Данные симптомы были выявлены у пациентов с алкогольной зависимостью и дефицитом питания. К концу 70-х годов прошло-

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Acute disseminated encephalomyelitis (AEM) and acute transverse myelitis (OPM) are autoimmune demyelinating diseases of the central nervous system. Two clinical observations of AEM and OPM developed after suffering acute coronavirus infection (SARS-CoV-2) are presented. Differential diagnosis was carried out with multiple sclerosis, encephalitis of an infectious nature, compressive myelopathy, and opticomyelitis. Both observations show an almost complete recovery of lost functions. The pathogenetic mechanisms of the development of AEM and OPM in patients with coronavirus infection are discussed. The onset of central nervous system dysimmune lesion in the context of coronavirus infection makes it necessary to monitor the clinical situation with the involvement of a neurologist for timely diagnosis and determination of therapeutic tactics that can reduce the degree of disability of patients.

A medical case of an acute demyelinating process in cerebrum caused by taking levamisole is presented. The issues of pathogenesis and differential diagnosis of levamisole-induced leukoencephalopathy with acute disseminated encephalomyelitis, multiple sclerosis, progressive multifocal leukoencephalopathy, and cerebral lymphoma are discussed.

Objective: to study the efficacy, safety and tolerability of agomelatine in mixed anxiety and depressive disorder.Patients and methods. Agomelatine was administered to 30 patients diagnosed with mixed anxiety and depressive disorder for 3 months. The patients' condition was assessed using a battery of psychometric methods – the Hamilton Depression Scale, the Hamilton Anxiety Scale, and a short form of the SF-12v2 quality of life questionnaire.Results and discussion. It was shown that agomelatine effectively reduces both symptoms of depression and anxiety, begins to have a therapeutic effect a week after the start of administration, however, the drug shows the best clinical effect when administered for a period of three months or more. The predictors of complete remission on agomelatine therapy in this sample were: the presence of sleep disorders (early and medium, but not late insomnia), a greater severity of somatized anxiety, the presence of complaints of decreased workplace performance and activity.Conclusion. Our study has shown that agomelatine is an effective, safe and well-tolerated drug in the treatment of mixed anxiety and depressive disorder.