The Influence of BDNF on Anhedonic Behavior in an In Vivo Model of Chronic Unpredictable Mild Stress
Depression is a significant global medico-societal concern. The serotonin system plays a pivotal role in modulating responses to acute stress and is implicated in the development of depressive and anxiety disorders. Recent research has increasingly focused on the potentially beneficial impacts of activating previously less-studied 5-HT4R and 5-HT7R subtypes on cognitive functions in the context of anxiety and depression. Additionally, intercellular adhesion molecules have been associated with the structural remodeling of neurons related to stress and mood disorders, potentially establishing functional connections with serotonin receptors. Furthermore, it is established that the exogenous administration of the neurotrophic factor BDNF can ameliorate the functioning of serotonergic neurons in the brains of rodents. This study aimed to investigate the influence of exogenously administered BDNF on the expression of 5-HT4R, 5-HT7R, and CD44 during a depressive-like state induced by chronic unpredictable mild stress (CUMS) in C57Bl/6 mice. The findings demonstrated that intranasal BDNF administration at a dose of 0.4 μg/kg for seven days sustained normal sucrose preference levels in animals following 21 days of CUMS exposure. While BDNF treatment did not impact the CUMS-induced reduction in mRNA expression of 5-HT4R and 5-HT7R across examined brain regions (cortex, hippocampus, and cerebellum), it did prevent the decrease in CD44 and TrkB receptor expression levels in the hippocampus. Additionally, it maintained BDNF expression levels in the cortex, although not in other brain regions. These results suggest that the application of BDNF in CUMS models has an antidepressant effect without directly affecting serotonin receptors, but probably by modulating 5-HT7R-CD44 interactions.
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 8 THE INFLUENCE OF BDNF ON ANHEDONIC BEHAVIOR.pdf | 987.86 KB |
In 2010, the first scientific study was published on genome-wide data on ancient DNA belonging to a male of the Paleo-Eskimo culture, who lived about 4000 years ago. Since then, advances in DNA techniques have made it possible to sequence hundreds and thousands of ancient genomes. Today, 13 years later, scientists have obtained genome data from more than 10,000 ancient humans, and data accumulation continues at an exponential rate. The vast majority of the studied ancient genomes were obtained from various places in the territory of Eurasia, which is distinguished by the huge diversity of its genes, cultures, and languages. Here we give an overview of the migration, mixing and continuity of the human population across the territory of Eurasia, starting from the period of its settlement by modern people and ending with the most mobile period in the history of mankind - the Iron Age.
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| 7 GENETIC HISTORY OF EURASIA BEFORE THE COMMON ERA.pdf | 601.82 KB |
Antisocial behavior (ASB) is a complex phenotype caused by the interaction between genetic and environmental factors. In past decades several genome-wide association studies (GWAS) and their meta-analyses identified up to 500 SNPs linked to externalizing pathology in Western Europeans. However, a question on their relevance to ASB in Eastern Europeans (i.e., Russians) remains open. Therefore, the present study aimed to replicate the effect of SNPs obtained from externalizing behavior GWAS meta-analysis on homicide behavior considering a possible modulating effect of social/lifestyle factors. We have selected top six SNPs (p < 10–21) from recent GWAS meta-analysis of ASB (Karlsson Linnér et al., 2021) including CADM2 rs993137, ZIC4 rs2279829, REV3L rs458806, XKR6 rs4240671, SORCS3 rs11596214, and BDNF rs6265. Subsequent genotyping was performed in the sample of homicide offenders (N = 227, 7% women) and corresponding control group (N = 254). A series of logistic regression (PLINK v.1.09) confirmed the association of REV3L rs458806 in the total sample (p = 0.044, OR = 1.346), while SORCS3 rs11596214, ZIC4 rs2279829, XKR6 rs4240671 demonstrated their association with criminal behavior in the subgroups including smoking, low-educated offenders, individuals with psychopathologies and conflicts in families. Our findings replicated the effect of REV3L, SORCS3, ZIC4, and XKR6 genetic variants on ASB in the Russian cohort under a moderating impact of social/lifestyle factors. However, the effect of social/lifestyle factors including sex, somatic diseases, and smoking on escalating antisocial behavior exceeded that of examined genetic variants.
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| 6 ANTISOCIAL BEHAVIOR- NATURE VS. NURTURE.pdf | 632.3 KB |
The focus of this review is on evaluating the contribution of various regulatory mechanisms of calcium metabolism to the execution of key microglial functions such as patrolling, migration, proliferation, polarization, as well as mitochondrial plasticity and inflammasome assembly. We address current issues on the regulation of calcium homeostasis in microglial cells and microglia-like cells (MLCs). A concise historical overview of microglia and MLCs is provided, followed by an analysis of their functioning in both normal and pathological conditions. We refer to the functional classification of various calcium channels and transporters expressed in the plasma membrane and endoplasmic reticulum of microglia along with elucidation of the mechanisms leading to elevated cytosolic Ca2+ concentrations in microglial cell upon their activation. Then, we discuss the contribution of NAD+-glycohydrolase/CD38 to the regulation of calcium homeostasis in microglia. The review highlights contemporary approaches for manipulating microglial calcium metabolism with potential implications for the treatment of neurodegenerative diseases and neuroinflammation. Additionally, we briefly mention on modern imaging methods for studying calcium signaling in microglia. Thus, we summarize current data that shed the light on the intricate interplay between calcium regulation and microglial function in brain (patho)physiology. It also offers insights into potential therapeutic strategies and visualization techniques in the context of diagnostics and treatment of neurodegenerative disorders and neuroinflammation.
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| 5 REGULATION OF CALCIUM HOMEOSTASIS IN MICROGLIA.pdf | 1.21 MB |
The ability to track some structural changes in enhanced green fluorescent protein (EGFP) by observing its fluorescence makes EGFP a convenient object for studying the protein denaturation process and the influence of some factors on denaturation, in particular, the presence of nanoparticles. In this work, we studied the EGFP fluorescence during its de- and renaturation processes, as well as the influence of the addition of iron oxide nanoparticles on EGFP fluorescence and these processes. Kinetic measurements of denaturation revealed some details of this process. During renaturation, we managed to achieve a 60% recovery of EGFP fluorescence compared to the native protein. We also demonstrated significant effects of the presence of iron oxide nanoparticles. Iron nanoparticles approximately doubled the denaturation rate and suppressed protein renaturation.
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| 4 STUDY OF THE ENHANCED GREEN FLUORESCENT PROTEIN.pdf | 934.24 KB |
1,2,4-trioxolanes were obtained by the ozonation of fish oil with a mixture of oxygen and ozone to study their physicochemical properties. The biological activity of 1,2,4-trioxolanes with betulin from birch bark extract in fish oil was evaluated under hypoxia and immobilization stress in rats. 1,2,4-trioxolanes composition led to LPO indexes normalization (malondialdehyde, Schiff bases, diene and triene conjugates), the activation of NADP/H and NAD/H-dependent enzymes (GR, G6PDH, LDH, AlDH), as well as SOD and catalase, under stress in rats. Thus, we estimated 1,2,4-trioxolanes with betulin in fish oil to regulate oxidative and energy metabolism under hypoxia and immobilization stress in rats. The findings show that studied composition can be useful to prevent and treat the diseases caused by oxidative stress.
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| 3 THE EFFECT OF 1,2,4-TRIOXOLANES WITH BETULIN IN FISH OIL.pdf | 1.14 MB |
The Republic of Sakha (Yakutia), located in the northeastern part of Russia, is characterized by an extremely cold climate, to which the indigenous people is adapted. Over the past decades, there has been a significant increase of the incidence of type 2 diabetes mellitus (T2DM) among the indigenous population. It is known that polymorphisms of the mitochondrial genome, in particular, the 16189C variant of hypervariable segment I (HVS-I), may contribute to the development of T2DM. The aim of the study was to assess the association of mitochondrial DNA (mtDNA) HVS-I polymorphisms with the type 2 diabetes mellitus in the Sakha (Yakut) population. Sequencing of HVS-I mtDNA in 102 patients with T2DM and 101 non-diabetic controls revealed 67 haplotypes and 64 SNP variants. There was no statistically significant difference in the frequencies of detected HVS-I polymorphisms and haplotypes between the two groups, which indicates the absence of a close association between HVS-I polymorphisms and T2DM in the Sakha population.
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| 2 SEARCH FOR ASSOCIATIONS OF MITOCHONDRIAL GENOME.pdf | 463.22 KB |
Overtraining syndrome (OTS) is a condition associated with prolonged dysfunctional adaptation to physical exercise and a long-term imbalance between training and recovery that results in decreased sports performance lasting from several weeks to months with serious consequences for the health of athletes. The problem of diagnosis and prevention of OTS remains relevant, as the diagnosis is often made retrospectively. Currently, no clear reliable biochemical or functional markers for early detection of OTS are described, and the features of pathogenesis of this syndrome remain unclear. The present overview describes the basic theories of OTS development, the main biomarkers and their diagnostic significance, as well as some novel parameters and methods that may be possibly perspective for early detection of OTS.
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| 1 OVERTRAINING SYNDROME- PECULIARITIES AND PERSPECTIVES.pdf | 428.94 KB |
Given the complexity and huge variety of human diseases and areas of medicine aimed at reducing or eliminating the negative consequences of various disorders in the normal functioning of complex systems, it is important to study these complex processes in model organisms. This article provides a short overview of human diseases and some applied areas of medicine in which some progress has been made through the study of model animals. In the future, new knowledge obtained on various animal models can be used to elucidate the etiology of disorders, with subsequent implementation in clinical medicine.
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| 12 MODEL ANIMALS USED IN BIOMEDICAL RESEARCH.pdf | 376.87 KB |
COVID-19 is a disease first reported in 2019 that claimed the lives of more than 6.5 million people worldwide, paralyzed transport links and locked the borders of many states for a long time. In 2023, 3 years have passed since, yet not all countries have fully recovered and lifted the restrictions, which, of course, highlights that COVID-19 has had a huge impact on all aspects of modern life. The pandemic has given a strong impetus to the development of science and the study of COVID-19 and infectious diseases in general around the world, many articles on COVID-19 have been published in the past 3 years. Particularly interesting was the fact that while some people were asymptomatic, had mild COVID-19, other patients required mechanical ventilation and even medically induced coma. In this regard, the study of the genetic factors contributing to the severe course of the disease, comorbidities and the individual response to drugs has become especially relevant. In our work, we consider the main genes and entire loci of chromosomes involved in the pathogenesis of COVID-19. Genes such as IFNAR2, TMPRSS2, ACE2, TYK2, DPP9, HLA, OAS3, ABO, 3p21.31 locus and 12q24.13 locus have been considered; in addition, the association of severe COVID-19 with diseases such as type 2 diabetes, cardiovascular disease and obesity was discussed.
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| 11 GENETIC BASIS FOR SEVERE COVID-19_0.pdf | 396.9 KB |
