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Tryptophan hydroxylases 1 and 2 (TPH1 and TPH2) play a key role in the synthesis of serotonin (5-HT), a hormone and neurotransmitter, in the peripheral organs and brain, respectively. The main aim of this study was to clarify the distribution of mRNA of the Tph1 and Tph2 genes in brain structures under normal conditions and after inflammation. The experiments were carried out on young (4 weeks old) male C57BL/6 mice. The animals were divided into three groups: intact, control, injected ip with saline, and injected ip with 2 mg/kg of bacterial lipopolysaccharide (LPS). Markers of inflammation, spleen mass and thymus mass were assayed 5 days after the saline or LPS administration. In the frontal cortex, hippocampus, striatum, hypothalamus, and midbrain the concentrations of 5-HT and its main metabolite, 5-hydroxyindole acetic acid (5-HIAA), and TPH activity were assayed using HPLC, while Tph1 and Tph2 mRNA were quantified using quantitative real-time RT-PCR. A dramatic increase of spleen mass and decrease of thymus mass 5 days after LPS administration was shown. A significant increase of 5-HT and 5-HIAA levels in the midbrain as well as decrease of 5-HIAA concentration and TPH activity in hypothalamus in mice treated with LPS and saline compared with intact animals was revealed. The highest concentration of Tph2 gene mRNA was observed in the midbrain in 5-HT neuron bodies, while this gene mRNA level was lower in 5-HT endings (cortex, hippocampus, striatum, and hypothalamus). Trace amounts of Tph1 mRNA was found in all studied brain structures in mice of the three groups. Thus, Tph1 gene expression in the mouse brain is too low to significantly affect 5-HT synthesis in normal conditions and during inflammation.

Aim    To compare serum concentrations of tryptophane (Trp) and its metabolites in subjects with no cardiovascular disease (CVD) and patients with СVD, including arterial hypertension (AH) and ischemic heart disease (IHD).Material and methods    This study included 131 participants; 58 participants (11 of them with documented peripheral atherosclerosis) were included into the AH group, 46 participants were included into the IHD group, and 27 participants with no signs of CVD were included into the control group. Plasma concentrations of Trp and its metabolites were measured by high-performance liquid chromatography in combination with a triple quadrupole analyzer.Results    Comparison of the three study groups revealed significant differences in concentrations of Trp (р=0.029), kynurenine (p<0.001), kynurenine/Trp ratio (p<0.001), quinolinic acid (р=0.007), kynurenic acid (р=0.003), serotonin (p<0.001), and 5‑hydroxyindoleacetic acid (5‑HIAA) (р=0.011). When the AH group was subdivided into subgroups without and with documented peripheral atherosclerosis, the intergroup differences remained for concentrations of kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, serotonin, and 5‑HIAA. Also, correlations were found between concentrations of Trp metabolites and laboratory and instrumental data, primarily inflammatory markers. Conclusion    Analysis of serum concentrations of Trp and its metabolites in CVD patients showed increases in kynurenine, kynurenine/Trp ratio, quinolinic acid, kynurenic acid, and 5‑HIAA along with decreases in concentrations of Trp and serotonin in the groups of AH, AH with documented peripheral atherosclerosis, and IHD.

The article presents the current literature on the role of serotonin in immunomodulation in multiple sclerosis, in particular, on the effect of serotonin on Th17-immune response and function of dendritic cells. The role of serotonin in the regulation of the gut-brain axis and the prospects for serotoninergic drugs as pathogenetic therapy in multiple sclerosis are discussed.

Aim: To investigate serotonin and catecholamine levels in people with paraphilic disorders and identify correlations between transmitter dysfunction and clinical signs of paraphilic disorders., Material and Methods: Fifteen men with paraphilic disorders were studied using clinical-psychopathological, sexological, biochemical and statistical methods., Results: There were an increase in the levels of serotonin and norepinephrine and a decrease in the concentration of DOPAC (3,4-dihydroxyphenylacetic acid) in the urine of patients with paraphilic disorders. The concentrations of serotonin and norepinephrine are correlated with obsessive disturbances. The level of DOPAC was associated with affective and dissociative disorders., Conclusion: The relationships between biochemical and psychopathological signs suggest a role of biological mechanisms in the organization of abnormal sexual behavior. Correlations between psychopathological phenomena and DOPAC indicate a key role of central dopamine in the pathogenesis of paraphilic disorders and disturbances of conscious regulation of behavior.

Changes in the activity of monoaminergic systems of the left and right hemispheres of the brain after acute hypoxia with hypercapnia were investigated in male albino mice. The concentrations of dopamine (DA), serotonin (5-HT) and their metabolites dihydroxyphenylacetic (DOPAC), homovanilic (HVA) and 5-hydroxyindolacetic (5-HIAA) acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. In the control mice not exposed to hypoxia with hypercapnia, a higher concentration of DA in the left cortex was detected. No asymmetry in the content of other substances has been identified in the investigated structures. Acute hypoxia with hypercapnia led to the right-sided increase of DA and 5-HT levels and to the left-sided reduction DOPAC in the cerebral cortex. Under the condition of hypoxia with hypercapnia, in the hippocampus, the left-sided increase of the DA content was revealed. In the striatum the contents of monoamines and their metabolites were insignificantly changed. It has been concluded that acute hypoxia with hypercapnia causes asymmetric changes in monoaminergic systems of the archicortex and the neocortex.

The influence of bone marrow autotransplantation on neurotransmitter structures of appendix vermiformis was studied. The study revealed that an increase in the number of neurotransmitter structures (mast and granular luminescent cells), having a high content of catecholamines and serotonin was noted in old rats in 40 min after bone marrow autotransplantation. In the center of vermiformis appendix lymphoid nodes reproduction cellular programmed differentiations having a high content of neuroamines are determined. In 2 hours after bone marrow autotransplantation their number decreases, the content of catecholamines and serotonin reduces as well. In the immunohistochemical reaction increase in proliferative activity of cells both in proper t. mucosa plate crypts and appendix vermiformis lymphoid nodules is observed up to 40 min of experiment. In 2 hours Ki-67 positive cells reduce both in t. mucosa and t. s/mucosa of appendix vermiformis.

Neuronal development of the majority of trochozoan animals with biphasic pelago-bentic life cycle starts from transient peripheral neurons, which do not belong to the central nervous system and are mainly located in the apical sensory organ and in the hyposphere. Some of these neurons are pioneer and send neurites that form a scaffold upon which the adult central nervous system later develops. In representative species of molluscs and polychaetes, immunolabelling with the antibodies against neurotransmitters serotonin and FMRFamide, and acetylated α-tubulin revealed that the structure of almost all early peripheral neurons is typical for sensory, most probably chemosensory cells: flask shape, and cilia at the end of the apical dendrite or inside the distal ampoule. Morphology, transmitter specificity, location and projections of the early sensory cells differ in trochophores of different species thus suggesting different origin of these cells. In polychaete larvae, pharmacological inhibition of serotonin synthesis in early peripheral neurons did not affect the development, whereas its increase resulted in developmental arrest and neural malformations, suggesting that early peripheral sensory neurons are involved in developmental regulation.

In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice. In mice of both groups, the Tph2, Ddc, Slc6a4, Htr2a, Htr3a, Htr5b, Slc18a2, and Bdnf genes were downregulated in the MRN and the Tph2, Ddc, and Slc6a4 genes were upregulated in the VTA. These changes were more significant in defeated mice. The Htr5b gene has first been shown to be involved in mechanisms of depression and pathology of aggressive behavior. In the defeated mice, the expression levels of the Htr4 and Aldh1b1 genes were increased in the MRN, and expression levels of the Maob, Htr4, Htr1a, and Slc18a2 genes were increased in the VTA, while the expression level of the Htr3a gene was decreased. In the HYP of aggressive mice the Maoa, Htr2a, Htr2c, and Creb1 genes were downregulated and the Htr6 gene was upregulated. In the defeated mice, the Maoa and Creb1 genes were downregulated and the Htr6 and Aldh1b1 genes were upregulated in the HYP. In the STR, the Htr1a gene was downregulated and the Htr7 and Bdnf genes were upregulated. The Htr1b gene was upregulated in the HIP. The coexpression of dopaminergic and serotonergic genes in the MRN and VTA in the control of pathological behaviors is discussed. Thus, the complex pattern of differential expression of serotonergic genes in brain regions developing under repeated agonistic interactions in mice in dependence on behavioral pathology have been observed.

Chronic social defeat stress (CSDS) leads to the development of mixed anxiety/depression-like state in male mice similar to those in humans. It has been shown that, under CSDS, the adult brain undergoes changes in the functioning neurotransmitter systems in different brain regions. In this experiment we are focused on the analysis of expression of genes encoding proteins related with the metabolism and receptors of serotonin, catecholamines, GABA and glutamate in the ventral teg- mental area which is important for regulation of motivations, emotions and is involved into mech- anisms of affective disorders. Mixed anxiety/depression-like state was generated in male mice by exposure to CSDS during 20 days. The collected samples of the ventral tegmental area were se-- quenced at JSC Genoanalytica,(http://genoanalytica.ru/, Moscow, Russia).'We found that genes, related with serotonin (Tph2, Maob, SIc6a4, Htr4, Htr1a) were upregulated but expression of Htr3a gene was downregulated in the ventral tegmental area of depressive mice in comparison with the control. Besides, upregulation of dopaminergic Th, Ddc, Slc6a3, Sic18a2, Drd2, and Maob genes was found while noradrenergic Dbh, Slc6a2, Adra2c, and Adra2a genes were downregulated. Ex- pression of GABAergic Gabral, Gabra2, Gabrg2, Gabrg], Gabrq, Gad], and Gad genes as well as glutamatergic Grial, Gria2, Grik2, Grm2, Grm5, and Slc 7a8 genes were increased under CSDS. Development of mixed anxiety/depression-like state under CSDS in male mice is accompanied by increased expression of genes coding the proteins participating in the metabolism and receptions of serotonergic, dopaminergic, glutamatergic and GABAergic systems. Expression of genes coding the adrenergic reception is decreased. It is supposed that Drd2 H Htr3a genes may play the key role in the synchronization of other genes of neurotransmitter systems.

This article presents the results of the study designed to determine the concentration of the neuromediator serotonin in the blood serum and tissue homogenates prepared from the polypous tissue harvested in the patients presenting with chronic polypous rhinosinusitis (CPR). The study included 51 patients with this pathology while 11 patients with chronic maxillary rhinosinusitis (CMR) and deflection of the nasal septum (DNS) made up the group of comparison. The serum serotonin levels were measured and compared in the patients of the main and both control groups. The results obtained give evidence of the significant inverse correlation between serotonin levels in the sera and tissue homogenates on the one hand and the history of allergic diseases in individual patients on the other hand.

In this study we investigated the effect of 5-HT on the spontaneous and miniature synaptic activity in lumbar motoneurons from isolated frog spinal cord using intracellular recording. 5-HT increased the frequency of the spontaneous and miniature postsynaptic potentials (mPSPs). The effect of 5-HT on different subpopulations of mPSPs was multidirectional: it increased the frequency of glutamatergic excitatoty mPSP by 18 % and decreased the frequency of glycinergic inhibitory mPSP by 28 %, but had no effect on the frequency of GABAergic inhibitory mPSP. The amplitude and kinetic parameters of any subpopulation of mPSPs did not change. The data obtained show that 5-HT regulates the probability of glutamate and glycine release from presynaptic terminals ending at the frog spinal motoneurons. 5-HT shifts the ba- lance between synaptic excitation and inhibition in the spinal neural network toward excitation. Thus, 5-HT participates in control of motor output and provides its facilitation.

The content of serotonin in the blood serum of rats with light desynchronizes and physical fatigue in different seasons was investigated ву enzyme immunoassay. It was found that long-term light deprivation and exercise to complete depletion lowered levels of serotonin in the blood serum of rats in the winter and increased that of the spring season. At the same time, a dark deprivation and physical activity had no effect on this indicator.

The article concerns study of the effects of a novel serotonin-modulating anticonsolidation protein (SMAP) being in a linear relationship with serotonin level, on embryogenesis of Lymneae stagnalis and Lewis sarcoma in hybrid mice Fl C57B2/6 X DBA. Inhibition of embryogenesis of Lymneae stagnalis on the stage of four blastomers and late blastula, lack of changes on the stage of trochofora and acceleration of metamorphosis under the effects of SMAP in a dose-dependent manner was observed. Short-term retardation (during the first 10 days) of development of Lewis sarcoma in mice and survival of 25% of transferring animals under high doses of SMAP was revealed. Cytostatic activity for high doses of SMAP and their effects on the duration of single phases of the cell cycle is proposed.

Serotonin functions as neurotransmitter in central nervous system and is involved in the regulation of vascular tone, gastro-intestinal motility and blood coagulation in the periphery. The appearance of new data on the significant correlation between serotonin levels in platelets and cerebrospinal fluid (Audhya et al., 2012) renewed interest in the hypothesis in which the platelet is seen as a model of cerotoninergic neuron. In our study, the levels of serotonin in platelets, serum and various brain regions of rats aged 6 and 24 months have been determined and comparatively analyzed. The method of high performance liquid chromatography was used. The decrease of serotonin level in platelets from 0.768 to 0.359 μg per 10(9) cells and its increase in the middle brain from 0.260 to 0.439 μg per 1 of wet weight have been clearly demonstrated in aging of animals. The differences in the content of serotonin in other parts of the brain and in the blood serum of young and old animals were statistically insignificant. Therefore, despite the attractiveness of the concept of platelet as a model of a neuron, the extrapolation of the data on platelet serotonin transport into neuronal ones requires caution, especially in the study of aging.

The review describes the influence of serotonin (5-HT) and its receptor, transporter SERT and nuclear factor Nf-kB on the immune function of the body, particularly in the digestive tract. The mechanisms of the synthesis, metabolism and catab. olism of 5-HT are characterized. The targets for serotonin on cell level are immunoactive cells--neutrophils, eosinophils, leukocytes, monocytes and dendritic cells. Receptor and non-receptor described mechanisms of action of peripheral serotonin are described. immunoactive cells express on their membrane 5 HT1A-5-HT1E-5-HT2A-5-HT3-, 5-HT4- and 5-HT7-serotonin receptor subtypes. Activation of these receptors modulate the release of TNF-α, secretion of interleukins IL-1β, IL-6, IL-8/CXCL8, IL-12p40. Mediators of the non-receptor mechanisms are transporter SERT, tryptophan hydroxylase-1 and nuclear factor Nf-kB. Target-genes for Nf-kB are genes encoding cytokines. The cooperation of non/receptory pathways involved 5-HT1A- and 5-HT3 receptors. It is concluded that the diversity of ways of peripheral serotonin on the immune function of the body are existed.

Analysis of the current state modeling of depression in animals is presented. Criteria and classification systems of the existing models are considered as well as approaches to the assessment of model validity. Though numerous approaches to modeling of depressive states based on disturbances of both motivational and emotional brain mechanisms have been elaborated, no satisfactory model of stable depression state has been developed yet. However, the diversity of existing models is quite positive since it allows performing targeted studies of selected neurobiological mechanisms and laws of depressive state development, as well as to investigate mechanisms of action and predict pharmacological profiles of potential antidepressants.

Recent studies considerably extended our knowledge of the mechanisms and physiological role of the interaction between different receptors in the brain. Current review summarizes data on the formation of receptor complexes and the role of such complexes in the autoregulation of the brain serotonin system, behavioral abnormalities and mechanism of antidepressants action. Particular attention is paid to 5-HT1A and 5-HT7 receptor heterodimers. The results described in the present review indicate that: i) dimerization and formation of mobile receptor complexes is a common feature for the members of G-protein coupled receptor superfamily; ii) 5-HT7 receptor appears to be a modulator for 5-HT1A receptor - the key autoregulator of the brain serotonin system; iii) 5-HT1A/5-HT7 receptor complexes formation is one of the mechanisms for inactivation and desensitization of the 5-HTIA receptors in the brain; iv) differences in the 5-HT7 receptor and 5-HTIA/5-HT7 heterodimers density define different sensitivity of pre- and postsynaptic 5-HTlA receptors to chronic treatment with selective serotonin reuptake inhibitors.

The activity of the hypothalamic-pituitary-thyroid (HPT) axis is controlled by the brain neurotransmitter systems, including the melanocortin signaling system. Pharmacological inhibition of type 4 melanocortin receptor (M4R) leads to disruption of the functioning of HPT axis and to reduction of the level of thyroid hormones. At the same time, the data on how prolonged inhibition of M4R affects this axis and on its role in regulation of M3R are absent. The relationship between the thyroid status and the activity of 1B-subtype 5-hydroxytryptamine receptor (5-HT1BR) is scarcely explored. The aim of this work to study the effects of chronic inhibition of M3R, M4R and 5-HT1BR induced by immunization of rats with BSA-conjugated peptide derived from the extracellular regions of these receptors on the thyroid status and the activity of thyroid stimulating hormone (TSH)-sensitive adenylyl cyclase signaling system (ACSS) in the thyroid glarid (TG) of the immunized animals. In rats immunized with the peptides K-[TSLHL WNRSSHGLHG11-25]-A of M4R, A[PTNPYCICTTAH269-280]-A of M3R and. [QAKAEE-EVSEC(Acm)-VVNTDH189-205]-A of 5-HT1BR levels of thyroid hormones such as fT4, tT4 and tT3 were significantly reduced. In rats immunized with M4R and M3R peptides, an increase of TSH was detected whereas in the animals immunized with 5-HT1BR peptide the level of TSH, on the contrary, was reduced. In the TG of rats immunized with M4R and M3R peptides, the stimulatory effects of hormones (TSH, PA-CAP-3 8) and GppNHp on adenylyl cyclase activity were attenuated, and the changes were most pronounced in the case M4R peptide immunization. After immunization with 5-HT1BR peptide the stimulatory effects of TSH, PACAP-38 and GppNHp were retained. Thus, the main cause of thyroid hormones deficit in rats immunized with M4R and M3R peptides was the decreased sensitivity of ACSS thyrocytes to TSH, whereas in rats iimunized with 5-HT1BR peptide the deficit of thyroid hormones was associated with decreased level of TSH. Our data on the negative impact of long-term immunization of rats with BSA-conjugated peptides derived from the extracellular regions of M4R, M3R.and 5-HT1BR on their thyroid status is a strong argument in favor of participation of these receptors and intracellular signaling pathways associated with them in the regulation of HPT axis.

The effects of prenatal stress on immunocytochemical reaction on serotonin (5-HT) in the dorsal raphe nucleus (DRN) of the brainstem were investigated in 7-day-old male rat pups exposed to impact of pain in the formalin test (a control is an injection of saline). A strengthening effect of prenatal stress on pain behavior was revealed in animals in the formalin test. Prenatal stress decreased the number of 5-HT-immunoreactive neurons as compared with that in prenatally non-stressed animals in both pups with inflammatory pain and the controls. There were no differences in the number of 5-HT-immunoreactive cells between pups with inflammatory pain and saline in both prenatally non-stressed animals and prenatally stressed ones. The data suggest that stress of maternal separation during the experiment hides the difference in immunocytochemical result in the rat pups with inflammatory pain and in the control. Thus, it was demonstrated for the first time that in 7-day-old rat pups the 5-HT-ergic neurons in DRN of the brainstem are a target of the prenatal stress.

The most common complication of diabetes mellitus of the type 1 (DM1) is a cognitive deficiency, which develops as a result of neurodegenerative changes in the brain. The aim of this work was to study the learning and spatial memory in rats with streptozotocin DM1 with different duration (1.5 and 6 months), as well as the activity of adenylyl cyclase signaling system (ACSS) sensitive to agonists of the serotonin and the dopamine receptors in the brain of diabetic rats. Our experiments demonstrated that rats with 1.5-months DM1 has no changes in spatial memory which were evaluated in a Morris water maze whereas in rats with 6-months DM1 the spatial memory and learning ability were decreased. The alterations of the regulation of adenylyl cyclase by agonists of types 1 and 6 serotonin receptors and type 2 dopamine receptors were found in both the 1.5- and 6-months DM1 which indicates their importance in the development of cognitive deficiency. Abnormalities in the. brain ACSS can be considered as key factors in the etiology and pathogenesis of cognitive dysfunctions in DM1. Hypothesized that cognitive deficiency occurs only in the later stages of DM1 due to alterations in the serotonin and dopamine signaling systems of the brain.

The influence of transcranial electromagnetic stimulation on the development of an active avoidance reflex with painful reinforcement in laboratory rats is investigated. It is shown, that an exposure of the rats' brain to electromagnetic radiation in the millimeter range ((λ = 5,6 and 7,1 mm), modulated as a series of low-frequency pulses, leads to a suppression of the development of the conditioned avoidance reflex occurred in 50% of cases. In other 25% of cases irradiation leads to inhibition of reflex development. Transcranial electromagnetic stimulation after intraperitoneal injection of the blocking agent of serotonergic receptors (kitryl) has no influence on reflex development. Electromagnetic brain stimulation does not influence reflex retention in the case when it has been acquired. Based on the data obtained it is assumed that transcranial electromagnetic stimulation promotes the development of serotonin, exerting an inhibiting effect on the formation of temporal bindings of the studied conditioned reflex.

The presence and localization of the serotoninergic and FMRFamidergic structures in the nervous system of the trematode Opisthioglyphe ranae, the marsh frog intestinal parasite, was studied using immunocytochemistry. The serotonin-immunoreactive nerve cells and fibers were revealed in the head ganglia, circular commissure, longitudinal nerve cords and their connective commissures, as well as around the oral and ventral suckers, oesophagus and genital pore. FMRF-specific immunoreactivity was observed in the head ganglia, longitudinal nerve cords and terminal parts of the reproductive system. The results obtained are discussed in light of the available data on the presence and functional significance of the above-mentioned neurotransmitters in trematodes.

The research of Cortexin and Pinealon within two models of stress, acute hypobaric hypoxia and mild hypothermia, within 18-month aged rats has been held. The peculiarities of peptide preparations' influence on behavior and neurochemical indeces have been identified. Cortexin shows a more pronounced effect on free radical processes and caspase 3 activity in brain than Pinealon. Both preparations forward an accumulation of adrenergic mediator within rats' brains in the model of acute hypobaric hypoxia, as well as serotonin within cerebrum cortex in the model of mild hypothermia, which may underlie their geroprotective effects.

In this work there is considered the possibility of correction of therapy for weakness syndrome in incurable patients with the use of drugs affecting dopamine and serotonin exchanges. It is showed that the use of 100 mg of ladasten, 16 mg of ondansetron orally per day and 50 mg of agomelatine per night is more effective in therapy for fatigue/weakness syndrome in incurable cancer patients compared to standard therapy.

The expression of serotonin transporter (5-HTT) was examined using the immunocytochemical method in the ventrolateral part of the nucleus of the solitary tract in Wistar rats in the early postnatal period (Days 5 and 10) in norm (n=10) and after prenatal serotonin deficiency (n=12). Temporary expression of the 5-HTT was demonstrated during the early postnatal period in the ventrolateral division of the nucleus of the solitary tract, that was more pronounced in the most caudal part of the ventral submucleus. It was shown that in the rostral part of ventral and lateral subnuclei, the number of neurons synthesizing 5-HTT was low and remained unchanged with age. In the caudal region of the ventral subnucleus, a large number of neurons synthesizing 5-HTT was found on Day 5 of postnatal period, that was significantly reduced with age. In the caudal region of the lateral subnucleus, a small number of neurons expressing 5-HTT was detected, that also decreased with age. It was found that in the caudal region of both ventral and lateral subnuclei, the level of 5-HTT expression was significantly higher than in the rostral region. Prenatal deficiency of serotonin resulted in a reduction of the number of neurons synthesizing 5-NTT in all the subnuclei investigated.

The aim of this study was to determine the distribution of GABAergic neurons in pneumotaxic center structures (parabrachial complex medial subnucleus and Kölliker-Fuse nucleus) in norm and in deficiency of serotoninergic system during the prenatal period of development in Wistar rats. Reduction of endogenous serotonin levels in fetal rats was achieved by tryptophan hydroxylase inhibition with para-chlorophenylalanine (PCPA), which was administered to female rats on Day 16 of gestation. Material was obtained from the area of the pons from experimental and control (intact) rat pups at early postnatal (Days 5, 10 and 12) and juvenile (Day 20) periods. At each time point, 5-6 animals were studied from both experimental and control groups. To demonstrate GABAergic neurons, antibodies against glutamate decarboxylase (GAD-67), the enzyme involved in its synthesis, were used. The results have shown that Kölliker-Fuse nucleus contained a population of GABAergic neurons at early postnatal period, the size of which was preserved until juvenile age. In parabrachial complex medial subnucleus during the early postnatal period, a small number of GABAergic neurons was detected, which was somewhat increased by juvenile age. Serotonin deficiency in pneumotaxic center structures lead to a reduction of the numbers of GABAergic neurons, GABAergic synapses and their clusters. A reduction of serotonin levels during the prenatal period may cause the disturbances in the inhibitory afferent signaling of the pneumotaxic center nuclei and lead to the changes of local inhibitory GABAergic networks in its nuclei, resulting in the disturbances of the inhibitory processes in the center structures.

Objective: The aim of the study was to determine the effect of the standard drug therapy of 95 patients with chronic cerebral ischemia (CCI) on the functional status of platelets as possible participants of microcirculation of the brain., Methods: Platelets were isolated from peripheral blood by centrifugation and examined at 24 hours after initiation of standard medical therapy including aspirin (100 mg). The cells were stimulated in vitro using adenosine diphosphate (ADP), epinephrine, platelet activating factor (PAF) and serotonin in an effective concentration (EC50) inducing in healthy individuals platelet aggregation in the range of 50 ± 5%. A study of platelet aggregation was carried out on aggregometer Chrono-Log (USA)., Results: Research included 95 patients with CCI 1-2 Stage--82 patients taking antiplatelet and antihypertensive drugs before hospitalization (main group), 13--did not receive these drugs during 7 days prior to hospitalization (comparison group). After start conservative treatment, only ADP induced platelet aggregation, which was similar (p > 0.05) with values in healthy individuals. The pharmacological inhibition of the functional activity of platelets other investigated agonists reproduced hyporesponsiveness of platelets. Against this background, in 34 (41.5%) patients at 24 hours after initiation of therapy occurred potentiation effects of PAF and epinephrine in the test in vitro; whereas the summation of the effects of serotonin and epinephrine on platelets was detected in 12 (14.6%) patients. The basis of this phenomenon may be strengthening effect of ADP secreted from dense-granules, additional stimulation by Gi-protein signaling system by epinephrine and Gq-protein by the action of PAF and serotonin., Conclusion: Response to the combined action of platelet agonists may be predictor of the risk of thrombogenesis at CCI.

Catalepsy usually is caused by imbalance of dopamine (DA) and serotonin (5-HT) systems of brain. The aim of our work was to verify if this imbalance plays an important role in the mechanism of hereditary catalepsy in mice. Maintenance of DA, 5-HT and their main metabolites--5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, homovanilic acid was determined in cortex, hypothalamus, hippocampus, striatum, substantia nigra and nuclei raphes in catalepsy-resistant AKR/J mice strain and catalepsy-prone CBA/LacJ mice strain and recombinant mice AKR/J.CBA-D13Mit76 (D13) strain. The latest strain was selected by transferring of a fragment of the chromosome 13 from CBA/LacJ carrying the main gene of hereditary catalepsy to AKR/J genome. There were no interstrain differences in concentration of biogenic amines and their metabolites in all brain regions. As a result of our work the hypothesis about the important role of 5-HT and/or DA systems of brain in the mechanism of hereditary catalepsy in mice was denied.

The role of disturbances in the hormonal signaling systems of brain and peripheral tissues in etiology and pathogenesis of diabetes mellitus (DM) of the types 1 and 2 is discussed. Available data confirming the hypothesis of central genesis of some forms of DM caused by disturbances in the brain neurotransmitter systems are presented. It is concluded that the study of disturbances in the hormonal signaling systems is a promising approach for development of new strategies of DM treatment, based on correction of these disturbances in the CNS and the periphery.

We found that the inhibitor of Rho-kinase fasudil selectively inhibited constriction of isolated rings of the aorta and mesenteric artery in rats in response to application of the agonists of 5HT2A-(DOI and TBC-2) and 5HT1A-receptors (8-OH-DPAT) and did not influence vasoconstriction induced by serotonin. We demonstrate for the first time that application of the agonists of 5HT2C-receptors (MK 212 and SCH 23390) did not influence the tone of "intact" vessels. The marked vasoconstrictory effect of the agonists of 5HT2C-receptors was observed in the vessels preconstricted due to angiotensin II or vasopressin. We found that the inhibitor of Rho-kinase did not influence negatively on MK 212 or SCH 23390-induced constriction of isolated rings of the aorta and mesenteric artery in rats. We suppose.that, in the presence of fasudil, serotonin induces constriction of vessels through the interaction with 5HT2C-receptors and signal transduction from these receptors does not involve Rho-kinase activity. We found that fasudil attenuated vasoconstriction induced by norepinephrine and vasopressin by 40%. We.demonstrated that tyrosine c-Src-kinase plays the most important role in signal transduction from 5HT-receptors because its effects are specific with relation to these receptors.

The article presents the results of the study including 60 patients with erectile dysfunction, divided into four age groups: 20-30, 31-30, 41-50, and 51-60. All patients have received biocomplex "NeiroDoz" for two months 2 capsules 2 times a day. Clinical effectiveness was evaluated according to the ICF and ICEF questionnaires and according to the patient's subjective evaluation of the clinical efficacy; the psycho-emotional status of patients and changes in the chronograms were also analyzed. In all men with erectile dysfunction, pronounced desynchronosis and psycho-emotional disorders were revealed. The use of complex "NeiroDoz" allowed to correct erectile disorders and psycho-emotional status of patients, as well as to restore normal chronorithms in all groups of patients, regardless of age and severity of erectile dysfunction.

To determine the effect of ischemic preconditioning upon myocardial serotonin and 5-hydroxyindolacetic acid (5-HIAA) dynamic in myocardial ischemia and reperfusion. 28 male Wistar rats anesthetized with urethane were randomly divided into 2 groups. In the control group (n = 13) rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. In the ex- perimental group (n = 15) ischemic preconditioning (3 x 3 min ischemia + 3 x 3 min reperfusion) before prolonged ischemia was used. Myocardial interstitial serotonin and 5-HIAA were measured using a microdialysis technique. Myocardial serotonin and 5-HIAA significantly increased af- ter ischemic preconditioning (p = 0.00298; p = 0.00187). In prolonged ischemia interstitial serotonin level was lower in the experimental group vs. control up to 20 min of ischemia (p < 0.05). We conclude that ischemic preconditioning increases interstitial myocardial serotonin, but inhibit serotonin increase in subsequent prolonged myocardial ischemia. After 20 minutes of reperfusion the lack of correlation between serotonin and 5-HIAA levels appeared which may be the evidence of serotonin uptake activation.

The aim of the work was to study the dependence of individual radiosensitivity of white and black rats on radiation. The rats under study were derived from a cross between black and white rats and called Ratus Ratus-Georgia. Comparative radiosensitivity of white (Wistar) and black rats was studied at a total exposure with sublethal and lethal doses (5, 7 and 9 Gy). Cumulative survival functions of rats, a spectrum of changes in some ethological parameters and content of serotonin and catecholamines in their brain structures were given as criteria of radiosensitivity. Survival rate of black and white rats is connected with changes in the composition and distribution of biogenic amines in the various brain structures, as well as with a decrease of locomotor and orienting-exploratory activity, on the one hand, and with increase of emotionality, stereotyped activity, passive defensive behavior of the rats, on another. Regression coefficients of dependence of survival functions on irradiation doses of black rats were rather higher than those of white rats after irradiation with doses in 5, 7 and 9 Gy. A change in the intensity of mortality with changes in radiation dose per unit depends on the synthesis of serotonin and on the number of sulfhydryl groups, deficiency of which is one of the important factors for white rats. Results of the study allow us to suppose that changes in the radiation sensitivity of rats after irradiation with sublethal and lethal doses are caused by consequences of radiation damage and by activation of the serotonergic system at the process of restitution after radiation injury. On the other hand, a higher radiation sensitivity of white rats in comparison with that of black rats is caused by low content of serotonin, thiols, melanin and other biologically active substances which are endogenous radioprotectors defining individual radioresistance.

The results of investigation of endocrinal and containing serotonin cells in gastric and rectal mucosa in 48 patients in nonspecific ulcerative colitis (NUC), are presented. In accordance to histochemical and immunohistochemical investigations, quantity of endocrinal cells and those, containing serotonin, in gastric and rectal mucosa is reducing, persistence of these changes depends on NUC severity.

The paper deals with study by the method of solid-phase indirect immunoenzyme analysis of levels of the novel serotonin-modulated anticonsolidation protein (SMAP) that is directly correlated with serotonin level as well as of biomarker cytochrome P-450 in the liver, gills, and brain of the eastern alburnoid (Alburnoides bipunctatus eichwaldi) caught in the rivers Khudat, Akstafachai, Kura, and Araks flowing at the territory of Azerbaijan. There was revealed a marked downregulation of cytochrome P-450 and SMAP in the liver and gills of the fish caught in the Akstafachai River relatively to values in the fish from the Khudat River not contaminated with pollutants. In the liver and gills in the fish from the Kura and Araks rivers, a significant differently directed changes of the cytochrome P-450 and SMAP levels were observed: downregulations of the cytochrome P-450 versus an upregulation of SMAP. In the brain of the fish from the River Akstafachai there was observed some downregulation of cytochrome P-450, whereas in fish from the Kura and Araks rivers--a significant upregulation of the SMAP level. The obtained results are analyzed from standpoint of processes of adaptation and disadaptation of aquatic organisms to impact of pollutants.

For the first time, the potential immunomodulators prostaglandin E2 and γ-aminobutyric acid (GABA) have been revealed in the plerocercoid Diphyllobothrium dendriticum, which is a parasite in the tissues and abdominal cavity of the Baikal omul Coregonus migratorius. The localization of immunomodulators in parasite tissues was compared with the location of typical markers of the nervous system (serotonin (5-HT) and FMRF-amide) and a marker of microtubules (α-tubulin). Prostaglandin E2 was revealed in the cells that are immunoreactive to α-tubulin and are situated in the cortical parenchyma outside the central nervous system (CNS). It is supposed that prostaglandin E2 is produced by the frontal glands and is carried out onto the tegument surface through specialized ducts. Immunoreaction to GABA was revealed in the central and peripheral nervous systems. GABA-ergic neurosomes, the neurites of which form a net on the surface of muscle layers and in the subtegument, were revealed in the cerebral ganglion and main nerve cords. The morphological characteristics for the identification of serotoninergic neurons in the CNS were described.

The changes in activity of monoaminergic systems of both the right and the left brain hemispheres of the BALB/c male mice after an acute hypoxia with hypercapnia were studied. The concentrations of dopamine, serotonin and their metabolites dihydroxyphenylacetic, homovanilic and 5-hydroxyindolacetic acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. The more high concentration of serotonin was revealed only in the cortex of the left hemisphere in control mice without hypoxia with hypercapnia. The asymmetry in dopamine level was not registered in all structures studied. Acute hypoxia with hypercapnia decreased the dopamine level in the striatum and the serotonin level both in the hippocampus and the brain cortex. The dopamine metabolites level was reduced in the striatum and in the brain cortex of hypoxed mice: both metabolites in the right brain cortex and only dihydroxyphenylacetic acid in the left br ain cortex. Serotonin metabolism was decreased in all brain structures studied after hypoxia with hypercapnia in mice. Therefore, serotoninergic system of the brain is more sensitive to acute hypoxia with hypercapnia than dopaminergic system.

Mechanisms of action of selective serotonin (5-HT) re-uptake inhibitors (SSRIs) on cardiac function in the ontogenetic aspect are not adequately explored. Object--Wistar rats: mature rats, pregnant females and their offspring at the age of 14 days. The positive inotropic reaction was detected to SSRIs fluoxetine (Flu) (0.1, 1.0, 10.0 μM) of the ventricles of adult rats, trittiko (SSRIs) exposed 14-day-old rats during the embryonic period. This is showed that contraction force was increased, the overall time contraction was decreased heavily due to more rapid relaxation. The effect on Flu is saved on the background of 5-HT (1.0 μM). The positive inotropic effect of 5-HT was decreased after the addition of all concentration of Flu. However, a dose-dependent increase of ventricle contraction force was revealed on Flu in mature rats. The positive inotropic effect of Flu, Flu on the back of trittiko in the left ventricle is higher than in the right; on the back of 5-HT is more pronounced in the right ventricle than in the left. The positive inotropic effect is decreased in the ventricles of 14-day-old when the concentration of Flu is increased.

Depression is considered to be an independent cardiovascular risk factor and it may worsen the symptoms of already established cardiovascular pathology such as coronary heart disease, chronic heart failure, stroke and hypertension. 3 key psychobiological mechanisms by means of which depression influences cardiovascular system: disbalance in stress response of endocrine system, hyperregulation of autonomic nervous system and immune disorders leading to dysregulation of acute phase proteins and proinflammatory cytokines release. In majority of studies in patients with depression and cardiovascular diseases it was shown that antidepressants improve the symptoms. By the way, in some studies controversial results were obtained. Future studies in this direction with involvement of cardiologists and psychiatrists should be held.

The review analyses the role of serotonin in the development of pathological processes in angiological patients, showing its negative role in aggravating chronic and acute ischaemia of various organs (brain, myocardium, extremities) both at the expense of vasoconstriction and due to an increase in blood platelet aggregation of blood platelets and erythrocytes, followed by analysis of clinical efficacy of naftidrofuryl) - serotonin 5-HT2 receptor antagonist. Results of numerous randomized trials confirmed its efficacy and safety in treatment of angiological patients, being superior to other vasotropic drugs (cilostazol, pentoxyphyllin, nicotinic acid).

A review of literature over the last two decades is presented. It is emphasized that psyachopharmacotherapy currently remains a main method of treatment of severe and moderate depression. Pharmacogenetic studies are directed mainly towards the identification of probable targets based on pharmacokinetcs and pharmacodynamics of andidepressants as well as the aspect of identification of probably predictors for treatment response.

Objective: To investigate the effect of olanzapine treatment on the ultrastructure of granulated platelets (GP) and vacuolated platelets (VP) and to find their association with platelet serotonin (PS) content and treatment efficacy in patients with schizophrenia., Materials and Methods: Platelets of 49 patients with attack-like schizophrenia treated with olanzapine and 31 healthy people were explored. Electron microscopic morphometry of GP and VP was performed to estimate the ultrastructural parameters of platelets. Microfluorimetry was used to measure PS content. RESULTS; The number of pseudopodies in GP and VP were lower after 28 weeks with olanzapine (-13%, p<0.01) as compared to the patients before treatment but the mean platelet area was not changed. Vv of granules was reduced in VP after 8 and 28 weeks of olanzapine (-13%, p<0,05). Vv of vacuoles was increased in GP in 28 weeks with olanzapine vs. 8 weeks with olanzapine (+16%, p<0.01) and in VP in 28 weeks of treatment vs.patients before treatment (+13%, p<0.01). In patients before treatment, Vv of vacuoles in VP was significantly higher in nonresponders as compared to the responders (+11%, p<0.05) and significantly correlated with PS content (r=0.26, p=0.04). The association between the number and Vv of vacuoles in VP before treatment and time point for positive treatment effect was found for the first time., Conclusion: Ultrastructural changes in Vv of vacuoles in platelets of schizophrenia patients treated with olanzapine are associated with serotonin metabolism and therapeutic efficacy.

Stress reactivity of the motivational system of defense can be assessed with the aid the cardiac defense response (CDR) - the reaction of the cardiovascular system to unexpected aversive unconditioned stimulus. The main objective of the study was revealing putative contribution of oscillatory systems of the brain into central pathogenic mechanisms of enhanced blood pressure (BP) stress-reactivity in naive patients with arterial hypertension (AH) of the 1st-2nd degrees (n = 17) and healthy control (n = 19) subjects. Using dynamic registration "beat-by-beat" arterial pressure, and oscillatory activity related EEG (64 channels) is estimated using the event-related synchronization/desynchronization (ERD/ERS). Along with abnormally high blood pressure in patients with hypertension background set significantly lower concentrations of serotonin blood platelets and increased tonic activation of the left hemisphere, reflected in the asymmetric reduction of delta- (2-4 Hz) and theta-1 (4-6 Hz) power in the central and parietal cortex in the hemisphere CDR of the patients are characterized by hyperactivity both short- and long-latency components of blood pressure. According to the dynamic analysis of the concomitant EEG, long-latency BP components may be accounted by, among other mechanisms, weakening of the descending ("top-down") inhibitory control, hypothetically implemented with the high-frequency EEG alpha (10-12 Hz) oscillations from the medial central-parietal cortex of both hemispheres of the brain.

Serotonin in cardiovascular system plays an important role in blood coagulation, allergy, and inflammation, as well as in blood vessel tone regulation. In this review, the mechanisms of serotonin effects upon the cells of blood vessels are considered and the list of main agonists and antagonists is presented. The signaling pathways activated by serotonin and their interaction in normal and pathological states are described.

An aim of the study was to investigate the effect of olanzapine treatment on platelet ultrastructure and to search for its association with serotonin metabolism in patients with schizophrenia. Platelets of 59 patients with chronic (attack-like schizophrenia) treated with olanzapine and 31 health people were explored. Based on the data on the platelet ultrastructure, authors studied the content of functionally activated vacuolated platelets (VP) and less active granular platelets (GP) as well of platelet serotonin (PS). VP content was higher in patients compared to the control group (+57%, p<0.001). After treatment for 8 and 28 weeks with olanzapine, it decreased and reached the control level (52% and 57%, respectively). There were significant negative correlations between % VP and PS before treatment (r= -0.30, p=0.02) and 8 week after treatment (r= -0.29, p<0.04) and a positive correlation between the decrease in % VP and increase in the PS levels during 8-week treatment (r=0.34, p=0.008). The association between increased platelet vacuolization and decreased PS content in schizophrenia was demonstrated for the first time. This association disappeared after treatment that led to the normalization of % VP and PS levels.

The description of the installation with inverted light is given as well as its software EthoStudio, which allows tracking the movements of any color animal in the water Morris maze (WMM) in high definition. The installation is based on the transmitted light technology (inverted light). The software gives possibility to estimate a wide range of learning indices. We have studied the statistic properties of three most widespread indices: latent time of platform finding, covered distance and the sum of distances to the center of the platform. The covered distance has shown the best statistic characteristics if compared to two other indices. The influence of polymorphism C1473G in the gene of the key serotonin synthesis enzyme, tryptophan hydroxylase 2, on the learning abilities of mice in WMM has been studied. Mice of the unique congenic lines B6-1473C and B6-12473G that differ by the polymorphic alleles C1473G have not demonstrated the association between the ability to learn and the genetically determined activity of tryptophan hydroxylase 2 in the brain.

Effect of serotonin-modulated anticonsolidation protein (SMAP) that has property of disturbing formation of memory trace in mammals and of learning and memory in teleost fish was studied in the model of active avoidance learning. The experiment was performed in three stages: (1) fry of carps Cyprinus carpio L. was injected intracerebrovenricularly with the SMAP protein at a dose of 0.3 μg/g; control individuals were administered with equal amount of the buffered saline for poikilothermic animals; (2) 24 h after the injection, fish were learnt during 8 sèances for 2 days the conditioned reflex of active avoidance; (3) 48 h after the learning the testing of the skill was performed. The administration of the protein was shown to lead to disturbance of reproduction of the skill in the fish: the latent time of the skill reproduction in experimental individuals exceeded that in control fish more than two times, while the number of individuals succeeding the task in the experimental group was non-significantly lower than in the control group. However, unlike mammals, injection of the SMAP protein in this model produced no effect on the process of learning in carps. Thus, there was first demonstrated the inhibiting effect of the SMAP protein whose concentration correlated positively with the content of the neurotransmitter serotonin in brain on consolidation of memory traces in teleost fish.

An overview of the results of studies on prolactin (PRL) is given. The molecular and genetic characteristics of PRL and its receptor (PRLR) are presented. The PRLR polymorphism in patients with tumors of the breast is described. Synthesized analogues of human PRL inhibited its peripheral effects. The vegetative nervous system modulate PRL secretion. PRL is a risk factor for breast and prostate cancer. The signaling mechanisms of PRL and its possible clinical use in therapy of breast cancer are characterized.

Experiments on the model of bilateral photothrombosis in prefrontal cortex showed that antibodies to glutamate one-time administered intranasally 1h after ischemic damage to the brain cortex lead to decrease of neurodegenerative influence of excitatory neurotransmitter after photothrombosis. It was showed the change of the level of dopamine, serotonin and their metabolites in hippocampus and prefrontal cortex.