Hypotensive Effects of Arginase Inhibition by L-Norvaline in Genetic Models of Normotensive and Hypertensive Rats.

The main effect of arginase inhibition after administration of L-norvaline is a decrease in BP. At the same time, norvaline causes various side effects in normotensive and hypertensive animals. In our experiments, L-norvaline was administered intraperitoneally (30 mg/kg) for 7 days to normotensive WAG rats (Wistar Albino Glaxo) and hypertensive ISIAH rats (Inherited, Stress-Induced Arterial Hypertension). In ISIAH rats, BP decrease was accompanied by an increase in diuresis, while in WAG rats, diuresis remained unchanged or little changed. At the same time, hypertensive rats demonstrated an increase of catecholamine content in the adrenal glands, while in normotensive animals, it was decreased. The differences in the effects of norvaline can be associated with different mechanisms of BP maintenance in normotensive and hypertensive animals. Normally, BP is maintained by the regulatory influences of the nitric oxide system. In hypertension, this system is weakened, and the hypotensive effects are probably achieved via increased diuresis.

Effect of Repetitive Transcranial Magnetic Stimulation on Serum Levels of Steroid Adrenal Hormones in Parkinson's Disease: Sex Differences.

In a parallel placebo-controlled study, we examined the effect of repetitive transcranial magnetic stimulation (rTMS) on serum concentrations of cortisol and dehydroepiandrosteron sulfate (DHEAS), and their relationships with clinical symptoms in men and women with Parkinson's disease. A 20-day course of real rTMS reduced the UPDRS and UPDRS III scores in patients with Parkinson's disease in comparison with the basal parameters (before rTMS), regardless of their sex. The level of cortisol did not change in men and women; at the same time, the content of DHEAS in men increased and before rTMS negatively correlated with the UPDRS scores. Sham rTMS had no effects on clinical parameters or hormonal levels. Possible mechanisms of sex-dependent differences in the effect of rTMS on the level of the neurosteroid hormone DHEAS are discussed.

[Clinical and neurophysiological effects of dual-target high-frequency rTMS over the primary motor and prefrontal cortex in Parkinson's disease]. / Klinicheskie i neirofiziologicheskie effekty terapevticheskoi sochetannoi vysokochastotnoi ritmicheskoi transkranial'noi magnitnoi stimulyatsii motornoi i lobnoi kory pri bolezni Parkinsona.

OBJECTIVE: To evaluate therapeutic effects of navigational dual-target high-frequency rTMS over the primary motor (M1, bilateral) and the left dorsolateral prefrontal cortex (DLPFC) on clinical dynamics of Parkinson's disease (PD) symptoms in a parallel placebo-controlled study. MATERIAL AND METHODS: The study included 46 patients randomized into equal therapeutic and placebo rTMS groups. Navigational therapeutic and placebo10 Hz rTMS was applied over the M1 and DLPFC areas (20 daily sessions, for 3 weeks). Assessment of the dynamics of clinical symptoms was performed using the MDS UPDRS scale (Parts I-IV) before the first session, immediately after 20 sessions, and 4-6 weeks after the rTMS course. Non-motor and mental symptoms were assessed using the Hamilton Depression Rating Scale (HDRS-17), Beck depression inventory (BDI-II), Depression, Anxiety and Stress (DASS-21) scales and the Mini Mental State Examination (MMSE). RESULTS: Significant therapeutic effects of rTMS compared to placebo were established: a greater decrease in overall score on the MDS-UPDRS scale (parts I-IV), a decrease in the severity of non-motor (part I) and motor symptoms (part III, with a large therapeutic effect for the symptoms of rigidity, bradykinesia and postural instability), as well as the severity of motor complications of dopamine replacement therapy (part IV). The effects of rTMS on motor symptoms persisted 4 weeks after the end of the stimulation course. It is also important to note significant positive dynamics in both rTMS and placebo groups in the form of comparable reduction in the severity of everyday motor symptoms (MDS-UPDRS part II), improvement of the total scores on MMSE, HDRS, BDI-II, DASS-21. CONCLUSIONS: The dual-target high-frequency rTMS over the primary motor cortex (bilateral) and the left dorsolateral prefrontal cortex has positive therapeutic effects on the motor and affective symptoms of Parkinson's disease, which are significantly stronger than that of the placebo stimulation.

Psychophysiological Analysis of Thymoleptic Effects of Xenon in Humans.

This pilot study was aimed at evaluation of the translational potential of xenon as a potential antidepressant. In placebo-controlled double-blind study, 14 healthy right-handed volunteers were randomly assigned to 15-min inhalation session of either gas mixture with xenon (25%Хе/30%О2/45%N2) or placebo (70%N2/30%О2) with simultaneous recording of 64-channel EEG. To assess the dynamics and nature of emotional activation in response to xenon and placebo, we analyzed both the intensity of positive and negative emotions and individual alpha peak frequency (iAPF) of EEG. We found that xenon in sub-anesthetic doses promoted positive emotional arousal, and that emotional response to xenon depended on individual neurophysiological endophenotype of alpha-activity (iAPF). The authors suggest that iAPF shifts can be used as a neurophysiological predictor of individual thymoleptic response to xenon.

[Exercise for depression treatment. Exercise modalities and types]. / Fizicheskaia nagruzka pri lechenii depressii. Rezhimy i vidy nagruzki.

The risk of metabolic disorders, including type 2 diabetes and cardiovascular diseases, is increased in depression, there is a decrease in life expectancy by 8-10 years. Pharmacotherapy is the first-line method in the treatment of depression. However, pharmaceutical-related side-effects and resistance to antidepressant pharmacotherapy create serious problems in treatment. Regular exercise not only weakens the symptoms of depression, increases aerobic capacity and muscle strength, but also has a positive effect on comorbid diseases. The purpose of this review is to answer the question, on which parameters of exercise the antidepressant effect depends. The review highlights the results of clinical studies of different types of exercises, intensities and modalities for the treatment of depression over the past 10 years. Because of the contradictory results of the studies, it is impossible to make final conclusions regarding the parameters of exercise. It is possible to say with high probability that in the treatment of depression, moderate and intense aerobic exercises with elements of strength exercises and a variety of coordination exercises more often lead to a positive effect than monotonous exercises with low intensity. It is possible that regular patient adherence to the prescribed exercise regimen is more important than the specific exercise type.

[Exercise for depression treatment. Physiological mechanisms]. / Fizicheskaia nagruzka pri lechenii depressii. Fiziologicheskie mekhanizmy.

This literature review considers meta-analyzes, systematic reviews and original research over the last decade addressing a comprehensive analysis of the antidepressant effect of targeted physical exercise and physical activity in general. Exercise is a promising non-pharmacological treatment for depression, showing effects that are comparable or may even exceed other first-line treatments of depression. The article introduces modern ideas about the mechanisms of depression and mechanisms of exercise effects on depression manifestations. The structures of the central nervous system, changing with the effective exercise-based treatment of depression, are indicated. Physical activity stimulates the secretion of growth factors, maintenance of angio-, synapto-, and neurogenesis. The regulation of antioxidant protection of neuronal mitochondria, a decrease in pro-inflammatory reactions and stress reactivity are also observed in response to regular exercise. Physical activity has a multimodal effect that stimulates biochemical pathways and restores neuronal structures disturbed in depression.

Therapeutic Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Neuroinflammation and Neuroplasticity in Patients with Parkinson's Disease: a Placebo-Controlled Study.

The parallel placebo-controlled study examined the therapeutic effects of dual-target repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (bilaterally) and the left prefrontal cortex (dorsolaterally) on spontaneous and mitogen-stimulating synthesis of pro- and anti-inflammatory cytokines by the blood cells and the level of brain-derived neurotrophic factor (BDNF) in blood serum of patients with Parkinson's disease. The significantly steeper positive clinical dynamics (assessed by UPRSD scale) observed in rTMS group in comparison with the placebo group was accompanied by a significant drop in spontaneous production of proinflammatory cytokines IFNγ and IL-17A. rTMS produced no significant effect on serum BDNF. The possible mechanisms of rTMS therapeutic action on the level of cytokines associated with neuroinflammation in patients with Parkinson's disease are discussed.

Variability of the Expression of Reference Genes in Samples of Human Olfactory Epithelium.

We analyzed variability of the expression of three reference genes in biopsy samples of the olfactory epithelium obtained from healthy volunteers. The expression of B2M, HPRT1, and CASC3 genes was analyzed by real-time PCR. The pairs of genes B2M-HPRT1 and B2M-CASC3 were found to possess minimum individual variability of expression and can be reliable candidates for the reference genes in analysis of gene expression in neural cells.

Frequency of 3' VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in Humans Predisposed to Antisocial Behavior.

Predisposition to antisocial behavior can be related to the presence of certain polymorphic variants of genes encoding dopaminergic system proteins. We studied the frequencies of allele variants and genotypes of variable number tandem repeat polymorphism in 3' untranslated region (3' VTNR) of the dopaminergic transporter SLC6A3 gene in Caucasian men committed socially dangerous violent and non-violent crimes. Alleles with 9 and 10 repeats were most frequent in both the control group and group of men predisposed to antisocial behavior. At the same time, the 10/10 genotype was more frequently observed in the group of men prone to antisocial non-violent behavior. Hence, the presence of certain variants of 3' VTNR polymorphism of SLC6A3 gene in men is associated with predisposition to certain forms of antisocial behavior.

[The Influence of Long-Term Meditation Practice on Early Emotional Processing in the Brain: an ERP Study].

The main aim was to study effects of long-term meditation practice on event-related brain potentials (ERPs) during affective picture viewing. The meditators' (N = 20), contrary to control (N = 20), did not demonstrate arousal-related increases in the mid-latency (200-400 ms) ERP positivity over the right hemisphere. We also found in the same time window stronger ERP negativity for meditators over central regions, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic detection of stimulus salience.

[The regulation of negative and positive emotions during picture viewing: an ERP study].

The study examines the effects of cognitive reappraisal on the event-related potentials (ERPs) to affective stimuli. Participants (n = 53) were asked either to attend affective images, or to down-regulate negative affect, or to up-regulate positive affect. Reappraisal of negative images was associated with attenuation of the P300 and late positive potential (LPP) over parietal regions, whereas reappraisal of positive images had no significant effect on ERP components. The weak P300 reduction correlated with high personality scores of negative affectivity. We assume that only down-regulation of negative emotions is associated with the changes in primary appraisals, and so far reflected in ERP modulation.

Effects of long-term meditation practice on attentional biases towards emotional faces: An eye-tracking study.

Attentional biases towards affective stimuli reflect an individual balance of appetitive and aversive motivational systems. Vigilance in relation to threatening information reflects emotional imbalance, associated with affective and somatic problems. It is known that meditation practice significantly improves control of attention, which is considered to be a tool for adaptive emotional regulation. In this regard, the main aim of the present study was to evaluate the influence of meditation on attentional bias towards neutral and emotional facial expressions. Eyes were tracked while 21 healthy controls and 23 experienced meditators (all males) viewed displays consisting of four facial expressions (neutral, angry, fearful and happy) for 10 s. Measures of biases in initial orienting and maintenance of attention were assessed. No effects were found for initial orienting biases. Meditators spent significantly less time viewing angry and fearful faces than control subjects. Furthermore, meditators selectively attended to happy faces whereas control subjects showed attentional biases towards both angry and happy faces. In sum we can conclude that long-term meditation practice adaptively affects attentional biases towards motivationally significant stimuli and that these biases reflect positive mood and predominance of appetitive motivation.

[Coupling of brain oscillatory systems with cognitive (experience and valence) and physiological (cardiovascular reactivity) components of emotion].

We investigated the coupling of EEG oscillators with cognitive (experience and valence) and physiological (cardiovascular reactivity) components of emotion. Emotions of anger and joy were evoked in healthy males (n = 49) using a guided imagery method, multichannel EEG and cardiovascular reactivity (Finometer) were simultaneously recorded. Correlational analysis revealed that specially distributed EEG oscillators seem to be selectively involved into cognitive (experience and valence) and physiological (cardiovascular reactivity) components of emotional responding. We showed that low theta (4-6 Hz) activity from medial and lateral frontal cortex of the right hemisphere predominantly correlated with the anger experience, high alpha (10-12 and 12-14 Hz) and gamma (30-45 Hz) activity from central-parieto-occipital regions of the left hemisphere--with cardiovascular reactivity to anger and joy, gamma-activity (30-45 Hz) from the left hemisphere in parietal areas--with cardiovascular reactivity to joy. The findings suggest that specially distributed neuronal networks oscillating at different frequencies may be regarded as a putative neurobiological mechanism coordination dynamical balance between cognitive and physiological components of emotion as well as psycho-neuro-somatic relationships within the mind-brain-body system.

[Features of brain oscillatory activity and cardiac defense in treatment arterial hypertensives].

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.

Influence of long-term Sahaja Yoga meditation practice on emotional processing in the brain: An ERP study.

Despite growing interest in meditation as a tool for alternative therapy of stress-related and psychosomatic diseases, brain mechanisms of beneficial influences of meditation practice on health and quality of life are still unclear. We propose that the key point is a persistent change in emotional functioning, specifically the modulation of the early appraisal of motivational significance of events. The main aim was to study the effects of long-term meditation practice on event-related brain potentials (ERPs) during affective picture viewing. ERPs were recorded in 20 long-term Sahaja Yoga meditators and 20 control subjects without prior experience in meditation. The meditators' mid-latency (140-400ms) ERPs were attenuated for both positive and negative pictures (i.e. there were no arousal-related increases in ERP positivity) and this effect was more prominent over the right hemisphere. However, we found no differences in the long latency (400-800ms) responses to emotional images, associated with meditation practice. In addition we found stronger ERP negativity in the time window 200-300ms for meditators compared to the controls, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic salience detection, based on amygdala functions.

Hypoactivation of reward motivational system in patients with newly diagnosed hypertension grade I-II.

In patients with newly diagnosed untreated grade I-II hypertension, EEG oscillations were recorded under conditions activation of the two basic motivational systems, defensive motivational system and positive reinforcement system, evoked by recall of personally meaningful emotional events. The 64-channel EEG and cardiovascular reactivity (beat-by-beat technology) were simultaneously recorded. At rest, hypertensive patients had significantly reduced platelet serotonin concentrations in comparison with healthy individuals. The patients experiencing emotional activation were characterized by significantly lower intensity of positive emotions associated with more pronounced suppression of EEG activity in the delta (2-4 Hz) and theta (ranges of frequency 4-6 and 6-8 Hz) oscillators in the parieto-occipital cortex (zones P and PO) in both hemispheres of the brain. The findings attest to insufficient function of the brain serotonin system and hypoactivation of the reward/reinforcement system in patients with primary hypertension.

Contribution of neurophysiological endophenotype, individual frequency of EEG alpha oscillations, to mechanisms of emotional reactivity.

We studied the relationship between individual alpha frequency (IAF) of EEG (neurophysiological endophenotype reflecting individual predisposition to efficacious cognitive and creative activity) and individual emotional reactivity. The psychophysiological study included healthy men in two models of evoked emotions - anxious apprehension (awaiting of inescapable aversive punishment) and discrete (opposite) emotions. Analysis of self-report, multichannel EEG, galvanic skin response, and cardiovascular reactivity showed that individuals with high IAF are characterized by predominance of parasympathetic influences in autonomic regulation circuit, proactive strategies of coping with inescapable threat, higher activity of positive emotional attitude and availability of memory traces about positive experience. Individuals with low IAF demonstrate predominance of sympathetic influences and maladaptive avoidance-like coping with inescapable threat and insufficiency of positive emotional activation mechanisms. It is suggested that IAF participates in the formation of individual emotional space and strategies of coping with emotional challenges.

Polymorphism of dopamine transporter gene DAT1 and individual variability of defense cardiac response in humans.

We evaluated association of BP stress-reactivity on the model of cardiac defense response in 45-70-year-old men with variable number of tandem repeat polymorphism in genes encoding dopamine transporter protein (DAT1) and serotonin transporter protein (5-HTTLPR). It was found that individuals carrying long allele variant (l) of DAT1 gene (l/l: allele l homozygotes) in the genotype in comparison with short variant (s) carriers (heterozygous genotype l/s) demonstrate hyperreactive profiles of cardiovascular stress reactivity characterized by a significant increase in the amplitude and duration of long-latency BP components in cardiac defensive response.

[Brain oscillations and individual variability of cardiac defense in human].

Cardiac defense response (CDR) is a specific dynamic pattern of the short- and long-latency cardiovascular reactivity (usually based on HR and/or arterial BP variables) in response an intense aversive unexpected stimulus. The CDR reflects activity of the defensive motivational system along with behavioral coping programs. The aim of the study was to estimate the putative contribution of brain oscillations into the central mechanisms of the CDR individual variability. EEG and cardiovascular concomitants of the CDR were estimated using the event-related synchroniza- tion/desynchronization (ERD/ERS) in different frequency bands as well as Finapres dependent variables obtained on the "beat-by-beat" basis. The first-ever findings evidenced significant cor- relations of the theta-2 (6-8 Hz) ERD/ERS with the sort-latency, whereas alpha-2 (10-12 Hz) ERD/ERS with the long-latency CDR variability. The hyperreactive long-latency systolic blood pressure CDR component was accompanied by the phase of deficient alpha-2 synchronization. It is suggested that upper theta oscillations are involved into central mechanisms scaling magnitude, whereas high frequency alpha oscillations may be responsible for the top-down inhibitory control of the short-and long-latency ABP stress-reactivity in the CDR.

[Individual preconscious affective biases to threatening and appetitive facial stimulus and cardiovascular stress-reactivity].

AIM: To investigate cardiovascular stress-reactivity in association with individual preconscious affective biases to threatening and appetitive facial stimuli. PATIENTS AND METHODS: Preconscious affective biases were assessed in healthy individuals (n = 38, mean age 28, 10 years, 1SD = 8.64) using a modified (masked) version of a pictorial emotional Stroop task (backward masking of the angry, fearful and joyful faces). RESULTS: It was revealed that individual preconscious bias to speeded up perception of angry faces correlates significantly with heightened anxiety, lowered platelet serotonin (5-HT) levels, sustained central overactivation of at rest (as indexed by lowered delta, theta, and beta-1 EEG power over frontal, central and posterior cortical areas) and exaggerated arterial blood pressure stress-reactivity during re-experiencing of personally relevant anger. CONCLUSIONS: considering uncovered associations, individuals with preconscious bias to speeded up perception of angry faces may be regarded as having enhanced risk to fall sick with essential hypertension, yet this perceptive bias could be seen as a putative neurobehavioral predictor of the risk.