Processes of intracellular and extracellular transport play one of the most important roles in the functioning of cells. Changes to transport mechanisms in a neuron can lead to the disruption of many cellular processes and even to cell death. It was shown that disruption of the processes of vesicular, axonal, and synaptic transport can lead to a number of diseases of the central nervous system, including Parkinson’s disease (PD). Here, we studied changes in the expression of genes whose protein products are involved in the transport processes (Snca, Drd2, Rab5a, Anxa2, and Nsf) in the brain tissues and peripheral blood of mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced models of PD. We detected changes in the expressions of Drd2, Anxa2, and Nsf at the earliest modeling stages. Additionally, we have identified conspicuous changes in the expression level of Anxa2 in the striatum and substantia nigra of mice with MPTP-induced models of PD in its early stages. These data clearly suggest the involvement of protein products in these genes in the earliest stages of the pathogenesis of PD.

Лейтрагин подавляет экспрессию цитокинов, включая интерлейкин-6, в модели «цитокинового шторма» у мышей линии C57BL/6Y с индуцированным острым респираторным дистресс-синдромом

Cardiotonic steroids (CTSs), such as digoxin, are used for heart failure treatment. However, digoxin permeates the brain–blood barrier (BBB), affecting central nervous system (CNS) functions. Finding a CTS that does not pass through the BBB would increase CTSs’ applicability in the clinic and decrease the risk of side effects on the CNS. This study aimed to investigate the tissue distribution of the CTS ouabain following intraperitoneal injection and whether ouabain passes through the BBB. After intraperitoneal injection (1.25 mg/kg), ouabain concentrations were measured at 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, and 24 h using HPLC–MS in brain, heart, liver, and kidney tissues and blood plasma in C57/black mice. Ouabain was undetectable in the brain tissue. Plasma: C_max = 882.88 ± 21.82 ng/g; T_max = 0.08 ± 0.01 h; T_1/2 = 0.15 ± 0.02 h; MRT = 0.26 ± 0.01. Cardiac tissue: C_max = 145.24 ± 44.03 ng/g (undetectable at 60 min); T_max = 0.08 ± 0.02 h; T_1/2 = 0.23 ± 0.09 h; MRT = 0.38 ± 0.14 h. Kidney tissue: C_max = 1072.3 ± 260.8 ng/g; T_max = 0.35 ± 0.19 h; T_1/2 = 1.32 ± 0.76 h; MRT = 1.41 ± 0.71 h. Liver tissue: C_max = 2558.0 ± 382.4 ng/g; T_max = 0.35 ± 0.13 h; T_1/2 = 1.24 ± 0.7 h; MRT = 0.98 ± 0.33 h. Unlike digoxin, ouabain does not cross the BBB and is eliminated quicker from all the analyzed tissues, giving it a potential advantage over digoxin in systemic administration. However, the inability of ouabain to pass though the BBB necessitates intracerebral administration when used to investigate its effects on the CNS.

For the first time, a liposomal form of a new original drug based on the Siberian musk deer preputial gland extract was obtained and characterized. An effective and scalable method of high-pressure homogenization was used for preparative extraction of liposomes from musk extracts. For the obtained liposomal product, such indicators as the quality of size distribution, homogeneity and the degree of inclusion of biologically active components were characterized using the methods of dynamic light scattering, transmission microscopy, preparative and analytical chromatography and chromatography-mass spectrometry. A homogeneous dispersion of musk liposomes with a uniform size distribution was obtained, with the maximum distribution values being achieved at 50 and 240 nm. The ζ-potential of the obtained nanoparticles of –35...–47 mV confirmed a high physicochemical stability of the developed liposomal dispersion. According to the gel filtration chromatography and mass spectrometry results, the degree of inclusion of the target musk extract components in the liposomes was 55–75% in terms of steroid and total protein values. The obtained quality indicators indicate that the developed liposomal composition of musk deer extracts can be used as a high-effective natural adaptogen.

Neuroinflammation can be an important factor of many disorders in central nervous system (CNS) including cognitive dysfunction, affective disorders, and addictive behavior associated with prenatal alcohol exposure and presented in early adulthood. In this study we used an experimental rodent model of prenatal alcohol (PA) exposure (consumption of a 10% ethanol solution by female Wistar rats throughout pregnancy), multiplex immunofluorescence analysis of interleukins (IL-1α, IL-1β, IL-3, IL-6, IL-9, and IL-12), tumor necrosis factor (TNF-α), and chemokine CCL5, as well as quantitative real-time PCR to assess the level of cytokine mRNAs in the prefrontal cortex of the sexually mature (PND60) offspring – male and female rats with prenatal alcohol intoxication and control animals. Significant decrease in the content of TNF-α and interleukins IL-1β, IL-3, IL-6, IL-9 was detected in the prefrontal cortex of male, but not in the female PA offspring. Importantly, PA males also showed decrease in the level of TNF-α mRNA in the prefrontal cortex by 45% compared to the control males, which may underlie the detected decrease in its content. Taken together, our study demonstrates that a number of neuroimmune factors are regulated in a sex-specific manner in the prefrontal cortex and are differentially affected in males and females by the prenatal exposure to alcohol. Sex factor must be taken into account when conducting further translational studies of the fetal alcohol spectrum disorders and developing new methods for prevention and therapy.

Проведено исследование содержания биологически активных веществ методом газовой хроматографии/масс-спектрометрии с применением дериватизации силилированием в прижизненно полученном мускусе кабарги. Проведено сравнение химического состава мускуса кабарги сибирской в природных и вольерных условиях. Выявлено влияние спектра питания кабарги на содержание биологически активных компонентов мускуса, прежде всего веществ андростероидного профиля. Подробно представлены результаты содержания наиболее значимых компонентов мускуса кабарги, имеющих биологические эффекты. Установлено, что увеличение разнообразия поедаемых кормов приводит к улучшению качественного состава биологически активных веществ мускуса, получаемого от самцов кабарги при вольерных условиях содержания.