Ключевым звеном патогенеза болезни Паркинсона (БП) является гибель дофаминергических нейронов в черной субстанции, вызывающая резкое снижение уровня дофамина в стриатуме головного мозга. Длительное терапевтическое применение предшественника дофамина L-ДОФА приводит к развитию тяжелых побочных эффектов и прогрессированию заболевания. Новый антипаркинсонический препарат, производный адамантана - гимантан (N-(2-адамантил)-гексаметиленимина гидрохлорид) обладает нейропротекторными и противовоспалительными свойствами. Цель работы: провести сравнительное изучение влияния производных адамантана - гимантана и амантадина - на параметры локомоторной активности мышей на разных стадиях развития паркинсонического синдрома (ПС). Материал и методы. Эксперименты проводили на мышах-самцах линии C57Bl/6 (n = 98) в возрасте 3-4 месяцев и массой тела 22-24 г. Стадии (начальную, среднюю и позднюю) ПС моделировали внутрибрюшинным введением нейротоксина1-метил-4-фенил-1,2,3,6-тетрагидропиридина (МФТП) однократно (в дозе 16 мг/кг, 30 мг/кг, 40 мг/кг), или многократно (4 раза по 12 мг/кг или 4 раза по 20 мг/кг с интервалом 2 часа). Гимантан и амантадин гидрохлорид (мидантан) вводили животным в дозе 20 мг/кг однократно за 30 мин до введения МФТП, или 4 раза при многократном введении нейротоксина. Развитие ПС оценивали по выраженности мышечной ригидности и изменению двигательной активности животных. Результаты. Показано, что введение гимантана и амантадина увеличивало длину пробега, число стоек мышей, а также снижало выраженность ригидности и степень нарушения координации движений животных с ПС, вызванным МФТП в дозе 16 мг/кг (однократно) и 4 × 12 мг/кг (многократно). При этом эффекты гимантана были более выраженными в сравнении с эффектами амантадина. Антипаркинсонический эффект обоих препаратов был слабее на промежуточной стадии ПС, вызванного однократным введением МФТП в дозе 30 мг/кг, и отсутствовал на поздней стадии ПС, вызванного многократным введением МФТП в дозе 4 × 20 мг/кг. Заключение. В сравнении с амантадином гимантан при предварительном введении более эффективно предупреждал снижение двигательной активности, нарушение координации движения и развитие ригидности животных на ранней стадии развития ПС.A key element in the pathogenesis Parkinson’s disease (PD) is death of dopaminergic neurons in substantia nigra, which leads to a sharp decrease in striatal concentration of dopamine. Long-term use of levodopa-containing drugs results in severe side effects and the disease progression. A new antiparkinsonian drug, the adamantine derivative, hemantane (N-(2-adamantyl)-hexamethyleneimine hydrochloride), has neuroprotective and anti-inflammatory features. Objective: To compare effects of hematane and amantadine on locomotor activity of mice at different stages of the parkinsonian syndrome (PS). Methods. Experiments were performed on C57Bl/6 male mice (n = 98) aged 3-4 months and weighing 22-24 g. The stages (early stage, mid-stage, and advanced stage) of parkinsonian syndrome (PS) were simulated in C57Bl/6 mice by intraperitoneal injections of a neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), either at a single dose of 16 mg/kg, 30 mg/kg, and 40 mg/kg, or repeatedly, 4 times at 12 mg/kg or 4 times at 20 mg/kg at 2-h intervals. Gimantan and amantadine hydrochloride (midantan) were administered to animals at a single dose of 20 mg/kg 30 minutes prior to MPTP administration or 4 times with the repeated administration of the neurotoxin. The development of PS was detected by muscle rigidity and changes in motor activity. Results. Administration of either hematane or amantadine increased the distance traveled and the number of rearings, and also reduced severity of the rigidity and impairment of movement coordination when PS was induced by a single injection of MPTP 16 mg/kg and repeated injections of MPTP 4 × 12 mg/kg. Furthermore, the effects of gimantan were more pronounced in comparison with the effects of amantadine. The antiparkinsonian effect of both drugs was weaker at the mid-stage of PS caused by a single injection of MPTP 30 mg/kg and was absent at the advanced stage of PS caused by repeated injections of MPTP 4 × 20 mg/kg. Conclusion. Compared to amantadine, the prior administration of gimantan more effectively prevented the decrease in motor activity, impaired coordination of movements and development of stiffness in animals at the early stage of PS.

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Parkinson’s disease (PD) is one of the key neurodegenerative disorders caused by a dopamine deficiency in the striatum due to the death of dopaminergic (DA) neurons of the substantia nigra pars compacta. The initially discovered A53T mutation in the alpha-synuclein gene was linked to the formation of cytotoxic aggregates: Lewy bodies in the DA neurons of PD patients. Further research has contributed to the discovery of beta- and gamma-synucleins, which presumably compensate for the functional loss of either member of the synuclein family. Here, we review research from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity models and various synuclein-knockout animals. We conclude that the differences in the sensitivity of the synuclein-knockout animals compared with the MPTP neurotoxin are due to the ontogenetic selection of early neurons followed by a compensatory effect of beta-synuclein, which optimizes dopamine capture in the synapses. Triple-knockout synuclein studies have confirmed the higher sensitivity of DA neurons to the toxic effects of MPTP. Nonetheless, beta-synuclein could modulate the alpha-synuclein function, preventing its aggregation and loss of function. Overall, the use of knockout animals has helped to solve the riddle of synuclein functions, and these proteins could be promising molecular targets for the development of therapies that are aimed at optimizing the synaptic function of dopaminergic neurons.

Corynebacterium spp. are part of the human microbiome, but can cause the development of inflammatory diseases of various localization. Purpose - to evaluate the relationship between pathogenic properties and resistance to antimicrobial drugs (AMD) of Corynebacterium spp. from patients with inflammatory diseases of the respiratory tract. Strains of Corynebacterium spp. isolated from patients with inflammatory diseases of the respiratory tract (99 pcs.) and practically healthy individuals (33 pcs.). Isolates were identified by mass spectrometric method (MALDI-ToFMS), their adhesive and invasive activity on Hep-2 cells, cytopathic effect (CPE) in CHO-K1 cell culture, and resistance to antimicrobial drugs (AMD) were determined. Indicators of adhesion (3.65±0.679(CFU±m)x102/ml), invasion (1.72±0.230 (CFU±m)x102/ml), cytotoxicity (69.1±3.8% of dead CHO-K1 cells ) Corynebasterium spp. strains isolated from patients are higher (p≤0.05) than similar indicators in practically healthy people. 90.9% of isolates from patients had resistance to AMD, in most cases (57.6±4.9%) resistance to only one AMP was noted, less often to two (25.2±4.3%), three or more (8.08±2.7%). According to the results of correlation-regression analysis, pathogenic properties (adhesiveness, invasiveness, cytotoxicity) of Corynebacterium spp. strains isolated from patients are in close direct relationship with resistance to AMD. This indicates the importance of identifying strains of non-diphtheria corynebacteria resistant to AMDs, which, under the influence of developing resistance to AMDs, can increase their pathogenic potential, moving from commensalism to parasitism.