Репозиторий Университета

Posttranscriptional gene regulation includes mRNA transport, localization, translation, and regulation of mRNA stability. CPEB (cytoplasmic polyadenylation element binding) family proteins bind to specific sites within the 3′-untranslated region and mediate poly- and deadenylation of transcripts, activating or repressing protein synthesis. As part of ribonucleoprotein complexes, the CPEB proteins participate in mRNA transport and localization to different sub-cellular compartments. The CPEB proteins are evolutionarily conserved and have similar functions in vertebrates and invertebrates. In the nervous system, the CPEB proteins are involved in cell division, neural development, learning, and memory. Here we consider the functional features of these proteins in the nervous system of phylogenetically distant organisms: Drosophila, a well-studied model, and mammals. Disruption of the CPEB proteins functioning is associated with various pathologies, such as autism spectrum disorder and brain cancer. At the same time, CPEB gene regulation can provide for a recovery of the brain function in patients with fragile X syndrome and Huntington's disease, making the CPEB genes promising targets for gene therapy.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2018 The Authors. We studied minor variants within two tick-borne encephalitis virus (TBEV) populations with a common ancestor: the mouse brain-adapted variant EK-328c and the tick-adapted variant M. High-throughput sequencing with custom amplicons from RTPCR viral RNA was performed on Illumina MiSeq 2*250 paired-end v2 chemistry. Using the LowFreq program (default settings) and Sanger-sequenced consensus as a reference, variants with an abundance of 1% and above within the studied populations were identified. Using the obtained data in the context of our previous studies, we concluded that TBEV variants, which are different from the major population phenotype and can become a major part of the viral population under favourable environmental conditions, can exist at abundances of less than 1% in the long-term. The comparison of our data with the literature allowed us to conclude that the laboratory variant EK-328c and variant M have similar SNV counts to TBEV variants from natural populations and some fast-evolving RNA viruses.

© Ima-Press Publishing House. All rights reserved. Cognitive impairment (CI) is common in patients with migraine; its causes and pathogenesis continue to be discussed. Some authors consider that migraine proper does not lead to decreased cognitive functions, neuroimaging changes in the brain white matter are asymptomatic in migraine; and CI in patients with this condition is caused by comorbidities (depression, anxiety disorder) and/or concurrent cerebrovascular and neurodegenerative diseases. Other authors report the pathogenetic role of migraine in the development of CI and the importance of the frequency of headache attacks and neuroimaging changes in the brain matter in migraine. The paper reviews clinical trials dealing with the prevalence, causes, and pathogenesis of CI in patients with migraine. It sets forth the current principles of prevention and treatment of CI in patients with this condition.

© 2018 ABV-Press Publishing House. All rights reserved. Background. Patients with the chronic migraine frequently present with memory and attention complaints. However, the prevalence and phenotype of such impairment in chronic migraine have not been studied. Objective-to evaluate the prevalence of the objective cognitive deficit in patients with chronic migraine and factors underlying its etiology. Materials and methods. We recruited 62 subjects with chronic migraine and 36 gender-and age-matched controls with low-frequency episodic migraine (not more, then 4 headache days per month) aged 18-59. All patients filled in the Hospital Anxiety and Depres sion Scale (HADS) and Sheehan Disability Scale. Cognitive function was assessed with the Montreal Cognitive Assessment (MoCA), Digital Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), and the Perceived Deficits Questionnaire (PDQ-20). Results. In this study 58 % of patients with chronic migraine complained of memory loss. Cognitive impairment was also found with PDQ-20. Objectively, we found a significant decrease in 90-second DSST results and RAVLT total recall and learning rate. In 40 % of subjects with chronic migraine scored lower than 26 points on MoCA. Patients with chronic migraine more frequently had lower DSST rates as compared to episodic migraine (odds ratio 5.07 (95 % confidence interval-1.59-16.17); p = 0.003). Depression and anxiety did not correlate with performance on cognitive tests. Chronic migraine (frequent headache) and longer headache history, but not depression, anxiety or medication overuse were independent predictors of cognitive impairment. Conclusion. Subjective and objective cognitive deficits are prevalent in the chronic migraine population. Most often memory and attention are impaired. Longer headache history and presence of chronic migraine are independent risk factors for cognitive impairment in patients with chronic migraine.

© 2018 Ima-Press Publishing House. All rights reserved.  The clinical efficacy and safety of interleukin-6 (IL-6) receptor blockade have been well studied, but the data on the impact of therapeutic inhibition of IL-6 on B cells are scarce and contradictory. Preliminary reports have shown that B cell function and a humoral immune response may be modulated by an IL-6 receptor inhibitor. Objective: to assess the effect of 12-month tocilizumab (TCZ) therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity. Subjects and methods. Examinations were made in 24 active RA patients (20 women and 4 men) (median age, 55 [49; 64] years; disease duration, 72 [24; 108] months; DAS28 5.8 [5.3; 6.3]; the patients were seropositive for rheumatoid factor (RF) (100%) and for anti-cyclic citrullinated peptide antibodies (87.3%). The patients received TCZ 8 mg/kg every 4 weeks. After 12 months of therapy, 54% of patients were categorized as good responders, 46% as moderate responders according to the EULAR response criteria. A control group consisted of 29 volunteers (21 women and 8 men; median age, 58.5 [53.0; 62.0] years). Peripheral blood lymphocytes were immunophenotyped at the time of enrollment and after 12 months. The absolute and relative counts of CD19+B lymphocytes, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgDCD27+), naive (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27) B cells, plasma cells (CD19+CD38+), and plasmablasts (CD19+CD38+++IgD-CD27+CD20-) were estimated using multicolor flow cytometry. Results and discussion. The relative and absolute counts of memory B cells (CD19+CD27+) (1.3 [0.9; 1.7]%, 0015 [0.001; 0.003]•10 9 /l), switched memory B cells (CD19+IgD-CD27+) (6.8 [3.6; 11.6]%, 0.01 [0.005; 0.02]•10 9 /l), and the absolute number of transitional B cells (CD19+CD38++CD10+IgD+CD27-) (0.00009 [0; 0.00028]•10 9 /l) were found to be lower in RA patients than in donors: 2.2 [1.1; 3.0]%, 0.003 [0.001; 0.007]•10 9 /l; 12.8 [9.3; 17.0]%, 0.02 [0.01; 0.04]•10 9 /l; 0.0001 [0; 0.0003]•10 9 /l, respectively (p<0.05 for all cases). After 12 months of TCZ therapy initiation, there were decreases in the relative and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) from 0.15 [0.1; 0.3] to 0.1 [0.01; 0.1]% and from 0.0003 [0.00007; 0.004]•10 9 /l to 0.0001 [0; 0.0003]•10 9 /l, respectively (p<0.05). At the same time, the relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) remained lower in RA patients than in donors: 1.0 [0.7; 1.2] and 2.2 [1.1; 3.0]%; 0.001 [0.006; 0.003]•10 9 /l and 0.003 [0.001; 0.007]•10 9 /l; 3.1 [1.1; 4.2] and 12.8 [9.3; 17.0]%; 0.003 [0.002; 0.006]•10 9 /l and 0.02 [0.01; 0.04]•10 9 /l, respectively (p<0.05 for all cases). Following 12 months of TCZ therapy, the numbers of other B-cell subpopulations were not considerably altered. When included in the study, the patients with RA showed correlations between the absolute count of memory B cells (CD19+CD27+) and the level of C-reactive protein (r=0.50; p<0.05); between the absolute count of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and the level of RF (r=0.41 and r=0.52; p<0.05). There were no correlations of B cell subsets with clinical and laboratory findings after 12 months of TCZ initiation. Conclusion. Immunophenotyping of peripheral blood B lymphocyte subsets showed the lower relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) in RA patients than in healthy donors. The found correlations between the counts of memory B cells and plasmablasts and the values of laboratory parameters in patients with high RA activity may suggest that B lymphocytes are involved in the pathogenesis of RA. There was a decline in plasmablast levels after 12 months of TCZ therapy.

© ABV-Press Publishing House. All rights reserved. Over a half of chronic pain (CP) patients present with cognitive complaints, which increase their disability and impact quality of life. The paper reviews objective impairments in memory, attention, processing speed and executive function demonstrated in the CP population. The paper also reviews common pathology underlying cognitive impairment and CP: neuroplasticity in the shared brain areas, neurotransmitter and other molecular mechanisms. Common mechanisms in CP and depression precipitating cognitive impairment are also discussed. The paper also compares the potential of different antidepressants to improve cognitive functions in depression and CP.

© 2018 ABV-Press Publishing House. All rights reserved. Background. Memory and attention deficits are prevalent in the chronic pain population. There are multiple common mechanisms in chronic pain and cognitive impairment. However, the presence, prevalence and clinical burden of such impairment are frequently underestimated. Objective: to evaluate subjective and objective cognitive deficits in patients with chronic migraine (CM). Materials and methods. We recruited 53 subjects with CM and 22 gender- and age-matched controls with low-frequency episodic migraine (a maximum of 4 headache days per month) aged 18-59. All patients filled in the HADS (Hospital Anxiety and Depression Scale) anxiety and depression scale and Pittsburg Sleep Quality Inventory (PSQI). Cognitive function was assessed with Montreal Cognitive Assessment (MoCA), Digital Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT) and the Perceived Deficits Questionnaire (PDQ-20). Results. 56 % of patients with CM complained of memory problems. Decreased cognitive function was also observed during self-assessment using the PDQ-20 questionnaire. Objectively, we found a significant decrease in 90-second DSST results and RAVLT total recall and learn ing rates. 44 % of subjects with CM scored lower than 26 points on MoCA. Most frequently we found impairments in attention (75 %), memory/delayed recall (50 %), language (50 %) and executive function (37 %). Depression and sleep quality correlated with only several parameters of cognitive tests. Conclusion. Subjective and objective cognitive deficits are prevalent in the CM population. Most often memory and attention are impaired. Cognitive complaints need to be carefully assessed, and treatment of such impairment may improve quality of life and decrease disability in CM.

© 2018 Russian Presidential Academy of National Economy and Public Administration. All rights reserved. This article uses oral history interviews to examine the memory of believers from Evangelical Christian-Baptist (ECB) churches regarding the requirements for women's external appearance as a reflection of their personal piety. While discussing believers' memory of the late Soviet period, the article demonstrates that these congregations focused almost exclusively on women. The conviction that believers were not to reflect the "outside world" in appearance was actually a double standard for women, since women's fashion choices have been much more dynamic than men's in the Soviet and post-Soviet periods. The article discusses the historical and social significance of the emphasis on women's appearance, arguing that both a high view of scripture and a nostalgia for the "Soviet past" perpetuated the patriarchal norms held by both men and women in ECB congregations. The authors then utilize a series of historical photographs from the 1940s to the 1970s to demonstrate the scope of the transformation of ECB believers' memory, which did not always accurately reflect late-Soviet reality. The authors conclude that the extensive changes in the social order in general and in women's fashion in particular in the post-Soviet period strengthened believers' impulse to isolate themselves from the immoral "outside world." By following the accepted norms for their external appearance, ECB women's appearance becomes a marker of their faith and a visible sign of their piety that is so highly prized by their community.

© 2018 Nutritec. All rights reserved. Specialized sports nutrition is one of the most important factors in the extension of the functional potential of athletes, providing adaptive resistance to physical stress, which determines the high physical performance and prolongs athletic longevity of the athletes. The study involved 30 skiers-racers (the average age of 19.5±1.8 years). 12 skiers of the main group within 21 days consumed a specialized food product, obtained on the basis of fermented milk whey containing amino acids, several vitamins, minerals and trace elements, live culture of lactic acid bacteria: L. lactis, L. thermophilus, L. bulgaricus (1.2 × 10s CFU/cm3). The control group consisted of 18 skiers, those taking the placebo (food starch of the same consistency). After a course of product intake, blood level of hemoglobin increased by 6%, of leukocytes - by 10% due to an increase in the number of granulocytes by 32%, and segmented neutrophils by 16% (p<0.05), there was a tendency to increase the number of red blood cells by 7% with a significant decrease in lymphocyte count by 19%. Erythrocyte sedimentation rate in blood of the skiers from the comparison group increased by 41% (p<0.05), while in the athletes of the main group it decreased by 16% (p>0.05). After product intake it has been established by the method of laser Dopplerflowmetry that there was a tendency to increase blood perfusion by 15%, a statistically reliable increase in the flux by 53%, which is based on the improvement of the internal mechanisms of microcirculation regulation. According to the mathematical analysis of cardiac rhythm, centralization of regulation decreased while the activity of an autonomous mechanism for controlling the work of the heart increased. The revealed functional changes ensured an increase of absolute (by 31%, p<0.05) and relative (by 33%, p<0.05) physical performance and aerobic endurance of skiers, contributed to the improvement of short-Term memory. The conclusion is made about the expediency of the intake of the specialized food product to enhance the adaptive capacity of athletes under the influence of systematic physical loads.

© 2018 Bentham Science Publishers. Background: It was previously shown that inactivation of gamma-synuclein which is a small soluble neuronal protein affects psycho-emotional status and cognitive abilities in knock-out mice. Objective: Determine the role of gamma-synuclein inactivation on memory performance in aging animals. Method: We used the passive avoidance test and acute amphetamine administration in aging gammasynuclein knock-out mice. Results: As a result, we found moderate aging-unlinked deficit of dopaminergic neurotransmitter system of gamma-synuclein knock-out mice. At the same time, the evidence of progressive synaptic vesicle trafficking machinery impairment was obtained. Conclusion: Therefore most likely these dysfunctions are associated with a reduction in the highefficient learning performance in tests that require intact working memory.