[Use of modern classification systems for complex diagnostics of Alzheimer's disease]. / Primenenie sovremennykh klassifikatsionnykh sistem dlya kompleksnoi diagnostiki bolezni Al'tsgeimera.

OBJECTIVE: To compare the content of ß-amyloid (Aß) peptides Aß40, Aß42, total and threonine phosphorylated 181 tau-protein in cerebrospinal fluid (CSF) of patients with the clinical diagnosis of Alzheimer's disease (AD). MATERIAL AND METHODS: The study was performed on 64 patients with a diagnosis of dementia and MMSE scores of 24 or lower. All patients underwent lumbar puncture. Aß40, Aß42, Aß42/40 ratio, total tau, phosphorylated tau at threonine 181 were determined in the CSF using a multiplex assay according to the manufacturer's protocol, the concentration was determined in pkg/ml. RESULTS: The preliminary diagnosis of AD was made in 3 patients (5%). As a result of the study of protein content in the CSF, signs of AD were detected in 48 (75%) people. The findings suggest that the diagnosis of AD is made 10-14 times less frequently than it should be according to the World Health Organization data. The discrepancy between clinical diagnosis and laboratory findings is confirmed by our study. CONCLUSION: Differences in the therapy of dementias and the development of new drugs targeting specific links in the pathogenesis of different types of dementias require accurate and complete diagnosis of dementias, especially AD, as the most common type of dementia.

Evaluation of the Optimal Number of Implanted Mesenchymal Stem Cells for the Treatment of Post-Traumatic Syrinx and Recovery of Motor Activity after Chronic Spinal Cord Injury.

The present work aims at determining the most effective dose (number) of mesenchymal stem cells (MSC) for its transplantation in order to treat chronic spinal cord injury (SCI) in mature Sprague-Dawley rats (n=24). MSC were obtained from bone marrow of 4-6-month-old Sprague-Dawley rats. Four weeks after SCI, MSC suspension (4 µl) was injected to experimental animals into the injured area in doses of 4×105, 8×105, or 106. Using MRI, diffusion tensor imaging (DTI), diffusion tensor tractography (DTT), immunohistochemistry, histological staining, and behavioral tests, we studied the effect of transplantation of MSC in different doses on the following parameters in rats with SCI: the size of lesion cavity and post-traumatic syrinx (PTS), glial scar formation, neuronal fibers remodeling, axonal regeneration and sprouting, vascularization, expression of neuronal factors, and motor functions. MSC administration improved motor function in rats after SCI due to stimulation of regeneration and sprouting of the axons, enhanced recovery of locomotor functions, reduction of PTS and the glial scar, and stimulation of vascularization and expression of the neurotrophic factors. The effects of MSC were dose-dependent; the most effective dose was 106 cells.

[Morphofunctional cerebral changes associated with development of suicidal behavior]. / Morfofunktsional'nye izmeneniya golovnogo mozga, svyazannye s razvitiem suitsidal'nogo povedeniya.

THE AIM OF THE STUDY: Was to identify the cerebral areas, which demonstrate the most significant structural changes and damaged functional activity in patients with suicidal behavior. The original studies, presented in PubMed database, were used to analyze the literature. Additional literature in the form of atlases, review articles and publications, written in related spheres, was used to interpret the results. The study identified the 69 cerebral regions, demonstrating significant changes and the structures with the most significant deviations among them were selected. The regions of cerebral grey matter, in particular basal ganglia (structures of striatum and limbic system), as well as selected regions of cerebral cortex, specifically frontal, insularis, singulate and parietal mostly were included in the list. The decrease in grey matter volume, changes of neuronal and glial density, special patterns of activity and variations of functional association with other cerebral regions are described within mentioned structures. The literature review found that there was a lack of postmortem examinations in suicidal cases. Advanced study of the described structures is required in cases of completed suicide using new research methods.

[Association of gene polymorphisms DRD3 rs6280, COMT rs4680 and HTR2A rs7322347 with schizophrenia]. / Assotsiatsiya geneticheskikh polimorfizmov rs6280 gena DRD3, rs4680 gena COMT, rs7322347 gena HTR2A s shizofreniei.

OBJECTIVE: To check the association of genetic polymorphisms rs6280 of the DRD3 gene, rs4680 of the COMT gene, rs7322347 of the HTR2A gene with schizophrenia. MATERIAL AND METHODS: The sample included 300 inpatients with paranoid schizophrenia. Inclusion criteria: age 18-50 years, established diagnosis «Schizophrenia, paranoid form¼, duration of psychiatric disorders not less than 5 years. The healthy control group consisted of 290 subjects. The association between polymorphisms and the study groups was assessed by logistic regression. RESULTS: The CC genotype of the rs6280 polymorphism is associated with schizophrenia (OR 3.37 (1.50; 8.03)). The TT genotype of the rs7322347 polymorphism is associated with controls (OR 1.83 (1.25; 2.68)). CONCLUSION: These analyses confirmed the hypothesis that the genetic polymorphisms rs7322347 of the HTR2A gene (p=0.006) and rs6280 of the DRD3 gene (p=0.004) were associated with the disease. The hypothesis of an association of the rs4680 polymorphism of the COMT gene could not be confirmed.

[Effects of diet on the gut microbiome in patients with depression]. / Vliyanie diety na mikrobiom kishechnika u patsientov s depressiei.

OBJECTIVE: To investigate the effects of diet on the gut microbiota and to assess the relationship of these factors with depression. MATERIAL AND METHODS: Microorganisms that predominate in depressed patients were identified and associations of the identified organisms with the patients' diet were performed. Fourteen depressed patients and 14 healthy volunteers with the same socio-demographic parameters were included in the study. The Hamilton Depression Scale, Generalized Anxiety Disorder Questionnaire, and the Center for Epidemiologic Studies Questionnaire were used. RESULTS: Erysipelatoclostridium and Clostridium innocuum species were 11.3 and 14.4 times higher in depressed patients compared with healthy controls. Fusicatenibacter saccharivorans, Faecalibacterium prausnitzii and Roseburia faecis species, as well as members of the genus Roseburia were statistically significantly more abundant in the healthy volunteers group (6.5, 2.14, 8.75 and 5.2 times more frequently compared to patients). The presence of these microorganisms was correlated with dietary components. CONCLUSION: Our study revealed groups of microorganisms that differ in healthy volunteers and depressed patients. The association of these microorganisms with the diet was shown, which partially confirmed the influence of a «healthy diet¼ on the development of depressive disorders.

[Molecular Biological Aspects of Depressive Disorders: A Modern View].

Depression is a serious mental disorder that affects more than 300 million people worldwide. Due to the lack of effective treatment methods, the pathogenesis of depression is necessary to study in order to understand its development and find new therapies. The review describes the main mechanisms of depression, including the monoamine hypothesis, impairment of the hipotalamic-pituitary-adrenal axis, decreased production of neurotropic factors, and neuroinflammation. Genetic correlations, gene polymorphisms, and epigenetic mechanisms are also considered. Common and different features of the etiology are analyzed for depression and depressive conditions associated with other pathologies (schizophrenia, Parkinson disease, and Alzheimer's disease). Modern experimental methods used to investigate the molecular mechanisms of depressive conditions are described with a focus on gene knockouts in laboratory animals and the CRISPR/Cas technology. Consideration is given to optogenetic and chemogenetic methods and analyses of genetic polymorphisms and their combinations. The data may provide for a better integral understanding of the modern ideas about the pathogenesis of depression as an isolated or comorbid disorder and the prospects in studying the mechanisms of depressive conditions.

Social and Cognitive Impairments in Rat Offspring after Ultrasound-Induced Prenatal Stress.

We studied the possibility of developing an autism model based on chronic prenatal psychological stress caused by variable frequency ultrasound 20-45 kHz. The offspring of female rats stressed during pregnancy demonstrated reduced time of social contacts in the social interaction test, increased anxiety in the open-field test, and memory impairment in the Morris water maze test in comparison with the control (intact) rat offspring. We also found a reducing trend in the BDNF gene expression in the amygdala in males of the experimental group. The results showed the possibility of developing the animal autism model based on prenatal stress.

Chronic Exposure to Ultrasonic Frequencies Selectively Increases Aggression in Rats.

We studied aggression in male Sprague-Dawley rats in a model of a depressive-like state induced by unpredictable treatment with ultrasonic waves with the frequencies of 20-45 kHz for 1, 2 or 3 weeks. We did not find any increase in the number of animals exhibiting aggression in the "resident-intruder" test after the treatment of any selected duration. However, the aggressive animals exposed to ultrasound exhibited the substantially increased number of attacks and their total duration as well as decreased latency of the first attack compared to the respective indices in the animals of the control group. Taking this into account, it is possible to suggest that the initial level of aggression increases in a model of ultrasonic chronic stress.

Three-Week Isolation Does Not Lead to Depressive-Like Disorders in Rats.

We studied the effects of social isolation for 1, 2 or 3 weeks on behavioral reactions of male rats. As social isolation is a common model for inducing depressive-like state in rodents, classical tests for depressive-like behavioral features were conducted: Porsolt forced swimming test and tests for anhedonia and social interest. None of the experimental groups showed statistically significant disorders in comparison with the control group kept under standard conditions. Thus, social isolation for up to 3 weeks did not cause behavioral abnormalities in male rats. Single housing can be used in other models of induction of depressive-like states, but the use of this paradigm as an independent model for the development of depressive-like behavior requires longer period of social isolation.

Effects of Chronic Exposure to Ultrasound of Alternating Frequencies on the Levels of Aggression and Anxiety in CBA and BALB/c mice.

Stress-induced changes in the behavior of CBA and BALB/c mice were studied after 3-week ultrasound exposure (22-45 kHz). The mice of both lines demonstrated increased aggression in the resident-intruder and social interest paradigms and reduced number of social interactions in the social interest test. Elevated plus maze test showed a decrease in anxiety level in CBA mice and an increase in this parameter in BALB/c mice. Chronic exposure to ultrasound induced an increase in aggression level in mice of both lines that was not directly related to changes in anxiety level.

Dynamics of the Development of Depressive-Like State in Rats Stressed by Chronic Exposure of Ultrasound of Variable Frequency.

We studied the effect of ultrasonic waves with a frequency of 20-45 kHz on behavioral reactions of rats after 7, 14 and 21 days of continuous exposure. A decrease in the number of social contacts in the social interest test was recorded in all groups, while lengthening of immobility time in Porsolt test was found only in the groups exposed to ultrasound for 2 and 3 weeks. Memory impairment in the new object recognition test was recorded only after 21 days of stressing. Chronic exposure to ultrasound of variable frequencies leads to the development of a depressive-like state in rats and the duration of exposure affects the specificity of the observed disorders. Different protocols of using of this model help to determine the stages of depressive-like condition in rats that can serve as a basis for the development of new methods of depressive disorders treatment.

[Genetic aspects of schizophrenia]. / Geneticheskie aspekty shizofrenii.

Schizophrenia is a disease with a complex non-Mendelian inheritance mechanism in most cases involving the combined action of a large number of genes. Identifying of genomic variations associated with schizophrenia endophenotypes has a great potential. This review describes genetic markers of the disease, current methods of their analysis, including genome-wide association study (GWAS). Certain genes with mutations that increase the risk of schizophrenia are described. Functional polymorphisms with phenotypic expression, which are significantly associated with clinical manifestation of schizophrenia, can serve as useful genetic markers. The authors highlight that currently there are no certain susceptibility genes. Further global research and search for markers in different population groups are needed.

Expression of genes encoding serotonin receptors and SERT in various brain structures of stressed rats after chronic exposure to ultrasound.

The expression of genes encoding serotonin receptors and serotonin transporter in emotiogenic structures of rat brain was shown to change after chronic stress with ultrasonic waves of varying frequencies. A QPCR-RT study revealed the increased expression of genes for SERT and 5-HT1B receptor and decreased expression of the 5-HT2A receptor in the prefrontal cortex of rats after chronic exposure to ultrasonic waves of varying frequencies. Gene expression was increased for SERT, but decreased for 5-HT1B, 5-HT2A, and 5-HT2B receptors in the midbrain of animals. The hippocampus was characterized by an increased expression of genes encoding SERT and 5-HT1A, 5-HT2A, and 5-HT2B receptors. Our results indicate that the exposure to this type of stress is followed by dysregulation in the serotoninergic system of the brain.

Effects of prenatal exposure to antibodies against brain-specific anion transporter on cognitive functions in rats.

We studied the effects of single intravenous injection of antibodies to brain-specific transmembrane anion transporter (BSAT1; 5 mg/kg) to pregnant rats (gestation day 10) on cognitive functions and behavior of their progeny. One of major functions of BSAT1 (or Oatp1c1) is specific transport of thyroxin across the blood-brain barrier. Female rats of two control groups were injected with non-specific Ig and 0.9% NaCl. The progeny of rats receiving monoclonal antibodies to BSAT1 demonstrated memory impairment in the Y-maze, novel object recognition test, passive avoidance test, and Morris water maze test in comparison with the control group. Our findings suggest that single injection of monoclonal antibodies to BSAT1 during the prenatal period was followed by cognitive impairments, which were probably related to thyroxin deficiency in the nervous tissue.

Effect of ultrasonic irradiation on the development of symptoms of depression and anxiety in rats.

Behavioral reactions of rats were studied under conditions of constant exposure to ultrasonic irradiation at a frequency of 20-45 kHz for 21 days. In rats subjected to ultrasound, impaired behavior in the social interest test and Porsolt forced swimming test was observed; the development of anhedonia in the sucrose preference test was revealed (manifested in the symptoms of depression). The effects of ultrasonic irradiation were abolished by an antidepressant fluoxetine, a selective serotonin reuptake inhibitor. Our results indicate that chronic exposure to ultrasonic radiation produces a modulatory effect on depressive symptoms in rats. These changes satisfy the requirements for experimental animals, which are used as a model of psychopathological processes.