Decrease of vanillin sucrose intake by victorious and defeated mice: development of anhedonia?

Hedonic reactions to various rewards play a key role in various forms of motivated behavior. The influence of repeated experience of social victories or defeats in daily agonistic interactions between male mice on voluntary consumption of vanillin sucrose solution used as hedonic reinforcer was studied. Intake of vanillin sucrose solution was shown to decrease in the winners and losers exposed to social confrontations as compared with the controls. Three days of deprivation failed to restore the intake of vanillin sucrose solution to the control level in the losers and did so in the winners. The results obtained imply that similar reaction of animals to a hedonic non-drug reinforcer may have different motivational origin depending on positive or negative social experience

Molecular implications of prolonged aggression experience: Th, Dat1, Snca and Bdnf gene expression in the ventral tegmental area of the victorious male mice

Th, Dat1, Snca and Bdnf were the genes whose mRNA levels in the ventral tegmental area of the midbrain were measured in male mice that were victorious in 20 daily agonistic interactions and in a group of such victorious mice that had later not been allowed to fight for 14 days. This experiment demonstrated increased Th, Dat1 and Snca but not Bdnf mRNA levels in the former group as compared to the controls. In the latter group, the expression of the Th and Dat1 genes was still enhanced, while the level of Snca mRNA did not differ from that in the controls. These findings suggest that positive fighting experience enhances the expression of the genes concerned with dopaminergic systems and this enhanced expression is preserved for a long time afterwards. Significant positive correlations were found between the level of aggression and Th and Snca mRNA levels in the winners

Anhedonia in the shadow of chronic social defeat stress, or When the experimental context matters

One of the core symptoms of major depression in human is anhedonia. For that reason, one of the main requirements towards experimental depression models is that they be able to demonstrate anhedonia in animals, that have been exposed to stressful events, and other behavioral changes attributable to a depression-like state. However, the results presented in the literature are contradictory: sweet solution intake, which is considered as a parameter of hedonic/anhedonic behavior in animals, responds quite differently to stressful situations in that it is either unaffected or increased or decreased. Different experimental designs used for the study of anhedonia in male mice exposed to chronic social defeat stress were tried to understand the reasons for so contradictory responses. Anhedonia appears as an abrupt reduction in sweet solution consumption in stressed animals and by failure to attain recovery after deprivation. However, it was also demonstrated that sucrose solution intake and preference strongly depend on the experimental context; that the possible critical factor may be prior acquaintance with the hedonic stimulus – or the lack whereof. Analysis of literature data and ours allowed us to conclude that the lack of a significant decrease in sweet solution intake in stressed animals is no evidence of lack of depression. This decrease is evidence of anhedonia only provided other symptoms of depression are present. Hedonic consumable intake can be decreased over various motivations, conditions or diseases, in particular, a high level of anxiety or pathological aggression

Application of the Sensory Contact Model for Pharmacological Studies under Simulated Clinical Conditions

The sensory contact model allows forming different psycho-pathological states (anxious depression, catalepsy, social withdrawal, pathological aggression, cognition disturbances, anhedonia, addictive states etc.) produced by repeated agonistic interactions in male mice and investigating the therapeutic and preventive properties of any drug as well as its efficiency under simulated clinical conditions. This approach can be useful for a better understanding of the drugs’ action in different stages of disease development in individuals. It is suggested that this behavioral approach and pharmacological designs may be applied for the screening of novel psychotropic drugs. 
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Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq

Chronic social defeat stress leads to the development of anxiety-and depression-like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. Most Rps, Rpl, Mprs, and Mprl genes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with "ribosomopathies.&quot

Mesenchymal stem cells in the treatment of ischemic stroke

Over the past two decades, multiple preclinical studies have shown that transplantation of mesenchymal stem cells leads to a pronounced positive effect in animals with experimental stroke. Based on the promising results of preclinical studies, several clinical trials on the transplantation of mesenchymal stem cells to stroke patients have also been conducted. In this review, we present and analyze the results of completed clinical trials dedicated to the mesenchymal stem cells transplantation in patients with ischemic stroke. According to the obtained results, it can be concluded that transplantation of mesenchymal stem cells is safe and feasible from the economic and biomedical point of view. For the further implementa-tion of this promising approach into the clinical practice, randomized, placebo-controlled, multicenter clinical trials are needed with a large sample of patients and optimized cell transplantation protocols and patient inclusion criteria. In this review we also discuss possi-ble strategies to enhance the effectiveness of cell therapy with the use of mesenchymal stem cells

Методичні рекомендації щодо розробки структури та змісту онлайн-курсів

The article looks into the matter of developing methodical recommendations for the structure and content of online courses. The research is dedicated to the analysis of peculiarities of developing the content of online systems and developing methodical recommendations for educational materials of online courses. The research considers the experts’ experience in preparing, structuring, and developing the content of online courses and answers to the volunteers who have agreed to test the educational materials of the course “Methods for Teaching Mathematics to Students in Technical Universities” http://formathematics.com/courses/imt/mnmtzvo-en/. The participants’ responses have allowed evaluating the quality of the developed course and detecting its insignificant drawbacks. The article discusses general requirements for the structure and content of the online course, means for the implementation of a testing subsystem, peculiarities of developing educational video content and education al materials in PDF format, issues of implementing forum and survey subsystems, as well as means of assessing learning outcomes. We have grounds to conclude that the quality of the course is determined by the range of factors, among which we point out the course organization based on weekly planning, implementation of a testing subsystem under conditions of extended functionality, creation of abilities to organize feedback.У статті розглядається питання розробки методичних рекомендацій щодо структури та змісту онлайн-курсів. Дослідження присвячене аналізу особливостей розробки контенту он-лайн систем та розробці методичних рекомендацій до навчальних матеріалів он-лайн курсів. У дослідженні враховано досвід експертів з підготовки, структурування та розробки контенту онлайн-курсів та відповіді волонтерів, які погодилися протестувати навчальні матеріали курсу "Методика навчання математики студентів технічних університетів" http://formathematics.com/courses/imt/mnmtzvo-en/. Відповіді учасників дозволили оцінити якість розробленого курсу та виявити його несуттєві недоліки. У статті розглянуто загальні вимоги до структури та змісту дистанційного курсу, засоби реалізації підсистеми тестування, особливості розробки навчального відеоконтенту та навчальних матеріалів у форматі PDF, питання реалізації підсистем форуму та опитування, а також засоби оцінювання результатів навчання. Маємо підстави зробити висновок, що якість курсу визначається комплексом факторів, серед яких виділяємо організацію курсу на основі потижневого планування, реалізацію підсистеми тестування в умовах розширеного функціоналу, створення можливостей для організації зворотного зв'язку

Altered Expression of Genes Associated with Major Neurotransmitter Systems in the Reward-Related Brain Regions of Mice with Positive Fighting Experience

The main neurotransmitters in the brain—dopamine, γ-aminobutyric acid (GABA), glutamate, and opioids—are recognized to be the most important for the regulation of aggression and addiction. The aim of this work was to study differentially expressed genes (DEGs) in the main reward-related brain regions, including the ventral tegmental area (VTA), dorsal striatum (STR), ventral striatum (nucleus accumbens, NAcc), prefrontal cortex (PFC), and midbrain raphe nuclei (MRNs), in male mice with 20-day positive fighting experience in daily agonistic interactions. Expression of opioidergic, catecholaminergic, glutamatergic, and GABAergic genes was analyzed to confirm or refute the influence of repeated positive fighting experience on the development of “addiction-like” signs shown in our previous studies. High-throughput RNA sequencing was performed to identify differentially expressed genes in the brain regions of chronically aggressive mice. In the aggressive mice, upregulation of opioidergic genes was shown (Oprk1 in VTA, Pdyn in NAcc, Penk in PFC, and Oprd1 in MRNs and PFC), as was downregulation of genes Opcml and Oprk1 in STR and Pomc in VTA and NAcc. Upregulation of catecholaminergic genes in VTA (Ddc and Slc6a2) and in NAcc (Th and Drd2) and downregulation of some differentially expressed genes in MRNs (Th, Ddc, Dbh, Drd2, Slc18a2, and Sncg) and in VTA (Adra2c, Sncg, and Sncb) were also documented. The expression of GABAergic and glutamatergic genes that participate in drug addiction changed in all brain regions. According to literature data, the proteins encoded by genes Drd2, Oprk1, Oprd1, Pdyn, Penk, and Pomc are directly involved in drug addiction in humans. Thus, our results confirm our earlier claim about the formation of addiction-like signs following repeated positive fighting experience in mice, as shown previously in our biobehavioral studies