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Valproic acid, beside its anticonvulsant action, is widely used as a mood stabilizer in the therapy of bipolar disorder. The potential antidepressant action of valproic acid has not been sufficiently characterized so far. The aim of the present study was to evaluate the antidepressant effect of valproic acid in an aldosterone model of depression. Subchronic treatment with valproic acid resulted in a reduction of the time spent in immobility in the forced swim test. In conclusion, the present study provides evidence on antidepressant effects of valproic acid using a classical behavioral approach for testing the efficacy of antidepressant drug in animal models.

Hypomethylating agent decitabine is being used in the treatment of certain types of leukaemia in combination with other anticancer drugs. Aberrant DNA methylation has been suggested to occur in pathological states including depression. Scarce data in male rats suggest antidepressant effects of decitabine. The main aim of our studies is to test the hypothesis that the inhibition of DNA methylation results in antidepressant effects in female rats. Before doing so, we decided to verify the effects of decitabine on DNA methylation in females. The findings demonstrate that the treatment with decitabine at the dose shown previously to inhibit DNA methylation in males, had no effect on total DNA methylation in two brain regions, namely the hippocampus and frontal cortex of female rats. In conclusion, the present study allows us to suggest that the effect of decitabine on DNA methylation in the brain is sex dependent.

Objective. The measurement of cortisol in hair became a popular and frequently used methodology in human stress research. This methodological approach, depending on the length of hair analyzed, allows to reflect cortisol secretion over prolong time periods in a retrospective fashion. There is a big variability in the experimental approaches to cortisol extraction used in individual laboratories. Moreover, there are many methodological details which are not described in most of the published papers, although they may be influential. The aim of the present study was to identify and optimize selected methodological steps of hair cortisol extraction.

Two clinical cases of perforation of a previously undiagnosed colon diverticulum in patients with coronavirus infection caused by the SARS-CoV-2 virus treated at the Hospital №1 of Nalchik. Both patients were elderly, overweight, had a lot of chronic concomitant diseases. Patients received hormone therapy and were targeted: the first patient twice (tocilizumab on the first day of hospitalization and olokizumab on the 7th day of inpatient treatment). The second patient received levilimab on the 3rd day of his stay in the hospital. A short time after targeting, both patients developed acute diffuse abdominal pain, the patients were transferred to the surgical department and operated on. During the operation, both patients were found to have previously undiagnosed diverticular disease, complicated by diverticular perforation and peritonitis on the background of immunosuppression. Both patients died. Thus, when using targeted therapy for patients with COVID-19, it is necessary to take into account that they may have previously undiagnosed chronic diseases that can cause fatal complications against the background of immunosuppression.

The relationship between subjective stress perception and the objective stress response to acute stress stimuli is not sufficiently understood. The aim of the present study was to test the hypothesis that the neuroendocrine response in socially evaluated cold pressor test (CPT) depends on the extent of perceived stressfulness of the stimulus. The test was performed in 24 healthy male volunteers. Subjective stress perception was assessed using nine visual analog scales. The subjects were divided to low and high stress perception groups according to the median split of the scores. Subjects with high stress perception exhibited slightly lower values of systolic blood pressure and lower overall concentrations of salivary cortisol compared to subjects with low stress perception. Salivary alpha-amylase activity did not show significant changes. Salivary aldosterone decreased in time in subjects with low but increased early after the test in subjects with high stress perception. Interestingly, salivary concentrations of the pro-inflammatory cytokine interleukin-1beta were considerably higher in subjects with high stress perception, particularly immediately before the test. The differences in salivary cortisol and interleukin-1beta were confirmed by the analysis with distress as a continuous covariate. Distress scores correlated negatively with salivary cortisol and positively with interleukin-1beta. The rate pressure product, which is a global measure of energy consumption by the heart, was significantly higher immediately before than after the stress exposure. The present findings show that concentrations of interleukin-1beta are a sensitive component of the stress response at the time before the stressful event.Lay summaryIt is generally expected that higher perceived stressfulness of a stimulus is accompanied by higher activation of stress-related systems. This study evaluating a combined psychosocial and physical stress situation in healthy men provides evidence that individual parameters of the stress response are differently related to perceived stress intensity. Subjects with high stress perception exhibited lower systolic blood pressure and salivary cortisol, higher interleukin-1beta, marginal differences in alpha amylase and aldosterone compared to subjects with low stress perception, which might be important for stress coping.

The aim of the present study was to test the hypothesis that vesicular glutamate transporter 3 (VGluT3) deficiency is associated with cognitive impairments. Male VGluT3 knockout (KO) and wild type (WT) mice were exposed to a behavioral test battery covering paradigms based on spontaneous exploratory behavior and reinforcement-based learning tests. Reversal learning was examined to test the cognitive flexibility. The VGluT3 KO mice clearly exhibited the ability to learn. The social recognition memory of KO mice was intact. The y-maze test revealed weaker working memory of VGluT3 KO mice. No significant learning impairments were noticed in operant conditioning or holeboard discrimination paradigm. In avoidance-based learning tests (Morris water maze and active avoidance), KO mice exhibited slightly slower learning process compared to WT mice, but not a complete learning impairment. In tests based on simple associations (operant conditioning, avoidance learning) an attenuation of cognitive flexibility was observed in KO mice. In conclusion, knocking out VGluT3 results in mild disturbances in working memory and learning flexibility. Apparently, this glutamate transporter is not a major player in learning and memory formation in general. Based on previous characteristics of VGluT3 KO mice we would have expected a stronger deficit. The observed hypolocomotion did not contribute to the mild cognitive disturbances herein reported, either., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Catecholamine effects via β3-adrenergic receptors are important for the metabolism of the adipose tissue. Physical exercise is a core component of antiobesity regimens. We have tested the hypothesis that voluntary wheel running results in enhancement of β3-adrenergic receptor gene expression in the white and brown adipose tissues. The secondary hypothesis is that dietary tryptophan depletion modifies metabolic effects of exercise. Male Sprague-Dawley rats were assigned for sedentary and exercise groups with free access to running wheels for 3 weeks. All animals received normal control diet for 7 days. Both groups were fed either by low tryptophan (0.04%) diet or by control diet (0.2%) for next 2 weeks. The β3-adrenergic receptor mRNA levels in response to running increased in the retroperitoneal and epididymal fat pads. The gene expression of uncoupling protein-1 (UCP-1) was increased in the brown, while unchanged in the white fat tissues. Unlike control animals, the rats fed by low tryptophan diet did not exhibit a reduction of the white adipose tissue mass. Tryptophan depletion resulted in enhanced concentrations of plasma aldosterone and corticosterone, but had no influence on exercise-induced adrenal hypertrophy. No changes in β3-adrenergic receptor and cell proliferation measured by 5-bromo-2'-deoxyuridine incorporation in left heart ventricle were observed. The reduced β3-adrenergic receptor but not enhanced uncoupling protein-1 gene expression supports the hypothesis on hypoactive brown adipose tissue during exercise. Reduction in dietary tryptophan had no major influence on the exercise-induced changes in the metabolic parameters measured., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To test the hypothesis that valproic acid treatment positively affects brain-derived neurotrophic factor (BDNF) expression and DNA methylation in the hippocampus and brain cortex of rats simultaneously treated with aldosterone., Methods: Male Sprague-Dawley rats (N=40) were treated for two weeks with valproic acid (100 mg/1 kg body weight/d) in drinking water and aldosterone (2 μg/100 g body weight/d) or placebo via subcutaneous osmotic minipumps., Results: Treatment with valproic acid did not modify BDNF gene expression in the hippocampus but reduced BDNF mRNA levels in the brain cortex. Valproic acid treatment marginally enhanced global DNA methylation in the frontal cortex. BDNF expression negatively correlated with DNA methylation in the hippocampus of valproic acid-treated rats. An unexpected finding was that aldosterone treatment significantly decreased global DNA methylation in the hippocampus., Conclusion: The effect of valproic acid on BDNF expression in the brain may depend on the extent of pathological changes present at the time of treatment onset. The observed negative correlation between BDNF expression and DNA methylation in the hippocampus of valproic acid-treated rats encourages further studies.

Several endocrine glands produce steroid hormones. Thanks to the work of chemists and biochemists, the main synthetic as well as metabolic pathways of steroid hormones were included in the textbooks more than 50 years ago and the classical endocrine gland functions were identified. Later on, evidence of steroid hormone effects beyond the classical endocrine gland function has been accumulating. Testosterone was shown to participate in the stress response and may influence coping with stressors. We have shown a decrease in testosterone concentrations in saliva in children undergoing a school exam compared to values on a non-exam school day. Testosterone has been associated with different cognitive functions in both adults and children. Circulating testosterone has been linked to negative symptoms of schizophrenia. Aldosterone is acting via mineralocorticoid receptors, which are thought to be fully occupied by glucocorticoids in the brain. Until now, an action of aldosterone in the brain has not been considered at all, because the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which would enable aldosterone to bind to receptors is absent in most of the brain areas. We have brought evidence that aldosterone can act in the brain and produce anxiogenic and depressogenic effects. To facilitate the translation of animal findings into clinical research, we have developed methodology for measurement of salivary aldosterone and obtained first data on a relationship between salivary aldosterone and trait anxiety. We have shown that salivary aldosterone concentrations reflect treatment outcome in patients with major depressive disorder., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)