The consequences of stroke include cognitive deficits and sensorimotor disturbances, which are largely related to mitochondrial impairments in the brain. In this work, we have shown that the mimetic ...of the ketogenic diet beta-hydroxybutyrate (βHB) can improve neurological brain function in stroke. At 3 weeks after photothrombotic stroke, mice receiving βHB with drinking water before and after surgery recovered faster in terms of sensorimotor functions assessed by the string test and static rods and cognitive functions assessed by the Morris water maze. At the same time, the βHB-treated mice had lower expression of some markers of astrocyte activation and inflammation (Gfap, Il-1b, Tnf). We hypothesize that long-term administration of βHB promotes the activation of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway, which leads to increased expression of antioxidant genes targeting mitochondria and genes involved in signaling pathways necessary for the maintenance of synaptic plasticity. βHB partially maintained mitochondrial DNA (mtDNA) integrity during the first days after photothrombosis. However, in the following three weeks, the number of mtDNA damages increased in all experimental groups, which coincided with a decrease in Ogg1 expression, which plays an important role in mtDNA repair. Thus, we can assume that βHB is not only an important metabolite that provides additional energy to brain tissue during recovery from stroke under conditions of mitochondrial damage but also an important signaling molecule that supports neuronal plasticity and reduces neuroinflammation.
Ageing is the most significant risk factor for cardiovascular diseases. l-Carnitine has a potent cardioprotective effect and its synthesis decreases during ageing. At the same time, there are ...pharmaceuticals, such as mildronate which, on the contrary, are aimed at reducing the concentration of l-carnitine in the heart and lead to slows down the oxidation of fatty acids in mitochondria. Despite this, both l-carnitine and mildronate are positioned as cardio protectors. We showed that l-carnitine supplementation to the diet of 15-month-old mice increased expression of the PGC-1α gene, which is responsible for the regulation of fatty acid oxidation, and the Nrf2 gene, which is responsible for protecting mitochondria by regulating the expression of antioxidants and mitophagy, in the heart. Mildronate activated the expression of genes that regulate glucose metabolism. Probably, this metabolic shift may protect the mitochondria of the heart from the accumulation of acyl-carnitine, which occurs during the oxidation of fatty acids under oxygen deficiency. Both pharmaceuticals impacted the gut microbiome bacterial composition. l-Carnitine increased the level of Lachnoanaerobaculum and Eubacterium hallii group, mildronate increased the level of Bifidobacterium, Rikinella, Christensenellaceae. Considered, that these bacteria for protection the organism from various pathogens and chronic inflammation. Thus, we suggested that the positive effects of both drugs on the mitochondria metabolism and gut microbiome bacterial composition may contribute to the protection of the heart during ageing.
Mildronate (MD) is a cardioprotective drug used for the treatment of cardiovascular diseases by switching metabolism from the fatty acids to glucose oxidation. This effect is achieved via inhibition ...of synthesis of L-carnitine (L-car), a common supplement, which is used for improving of fatty acid metabolism. Both MD and L-car have similar neuroprotective effect. Our goal was to investigate the effect of two drugs on the cognitive parameters of mice under different conditions (aging and lipopolysaccharide (LPS)-induced inflammation). We showed that L-car partly improved the memory and decreased the extent of mtDNA damage in the hippocampus of mice with the LPS-induced inflammation. L-car induced mitochondrial biogenesis and mitophagy in the Nrf2-dependent manner. Both MD and L-car upregulated expression of genes involved in the mitochondrial quality control. In 15-month-old mice, MD improved long-term and short-term memory, reduced the extent of mtDNA damage, and decreased the concentration of diene conjugates in the hippocampus in the Nrf2-independent manner. L-car as a Nrf2 activator had a better neuroprotective effect by normalizing mitochondrial quality control in the reversible cognitive impairment caused by the LPS-induced inflammation, while MD had a better neuroprotective effect in the irreversible cognitive impairment in aged mice, possibly due to a deeper restructuring of metabolism and reduction of oxidative stress.
Mitochondrial dysfunction in the ischemic brain is one of the hallmarks of stroke. Dietary interventions such as the ketogenic diet and hydroxycitric acid supplementation (a caloric restriction ...mimetic) may potentially protect neurons from mitochondrial damage induced by focal stroke in mice. We showed that in control mice, the ketogenic diet and the hydroxycitric acid did not impact significantly on the mtDNA integrity and expression of genes involved in the maintenance of mitochondrial quality control in the brain, liver, and kidney. The ketogenic diet changed the bacterial composition of the gut microbiome, which via the gut-brain axis may affect the increase in anxiety behavior and reduce mice mobility. The hydroxycitric acid causes mortality and suppresses mitochondrial biogenesis in the liver. Focal stroke modelling caused a significant decrease in the mtDNA copy number in both ipsilateral and contralateral brain cortex and increased the levels of mtDNA damage in the ipsilateral hemisphere. These alterations were accompanied by a decrease in the expression of some of the genes involved in maintaining mitochondrial quality control. The ketogenic diet consumption before stroke protects mtDNA in the ipsilateral cortex, probably via activation of the Nrf2 signaling. The hydroxycitric acid, on the contrary, increased stroke-induced injury. Thus, the ketogenic diet is the most preferred variant of dietetic intervention for stroke protection compared with the hydroxycitric acid supplementation. Our data confirm some reports about hydroxycitric acid toxicity, not only for the liver but also for the brain under stroke condition.
This study is focused on the quantification of dust load on snow cover and chemical elements content in the solid phase of snow cover in the impacted areas of cement plants (the south of Western ...Siberia). Applying the instrumental neutron activation analysis, we identified chemical composition in the samples of the solid phase of snow cover. The results demonstrated that the dust load corresponded to the permissible pollution levels in the living zones. Dust pollution level varied from moderately hazardous to highly hazardous in the north-western impacted zone of the cement plants and raw material open pits. It was found that the predominant chemical element is Ca, as well as a group of rare-earth (Yb, Tb, Sm, La, Ce, etc.) elements in the solid phase of snow cover from the impacted zone of the cement plants.
This paper shows the results of environment assessment within some cities of Western Siberia (Omsk, Tomsk, Kemerovo) impacted with different types of industries and fuel energy. This assessment is ...made on the basis of chemical composition study of particulate matter deposited in the snow cover. It is determined the marker elements (heavy metals, radioactive, rare and rare-earth elements) in the particulate phase of snow, which is reflected the specific emissions from different types of industries (oil-refinery, petrochemical plants, mechanical and instrument engineering factories, brickworks, thermal power plants) in the urban areas.
The paper considers the problems of applying the Russian as a foreign language teaching technique for teaching literature at pre-university department. In spite of the reduced scope of additional ...educational program in literature as provided for by the new requirements, in this audience, studying the Russian writers’ works corps is coupled with difficulties of both linguistic and mental nature. The teaching starts in groups having A1 mastery level of Russian, and, alongside with the non-mother tongue, the attendees have to master a course of Russian literature ranging from folklore and Old Russian literature to that of the 20th century within an incomplete academic year. The specific character of students’ audience and program requirements prescribe the necessary use of the main principles of RFL teaching – communicative, linguistic, didactic and psychological ones. The authors of the paper pay a special attention to practical application of the said principles giving numerous examples of study assignments and exercises of various types. The paper can be targeted to RFL teachers, students of philology and to everyone interested in problems of techniques of teaching literature in a non-mother tongues.
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