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Objective: to study the main components of the formation of impaired left ventricular diastolic filling in adolescents with myocardial pathology. Materials and methods. The study involved 110 adolescents with myocardial pathology aged 13–18 years, of which 40 — with heart rhythm disorder, 40 — with dysplastic cardiomyopathy, 30 — with primary hypertension. Morphological and functional parameters of the heart were studied using ultrasound according to standard procedure. Left ventricular diastolic function has been studied in the pulsed wave Doppler mode with transmitral flow mapping from the apical access of four-chambered heart. For an adequate assessment of left ventricular diastolic function and detection of its earliest disorders, adolescents underwent tests with isometric exercise. Based on these results, adolescents were divided in terms of the E/A ratio. In order to identify common latent factors that explain the correlation between indicators, we have used the factor analysis, namely, the principal component analysis. All statistical procedures were performed using application packages Statgraphics Centurion. Results. On the initial stages of formation of diastolic dysfunction of the left ventricular myocardium in adolescents, a significant role is played by a number of factors, which can be conditionally defined as the geometric, functional and neurohumoral factors consistently included in the pathological process. Thus, during the formation of left ventricular diastolic dysfunction type 1, the number one is neurohumoral factor, namely, the activation of the sympathoadrenal system, then peripheral vascular tone is being involved in the pathological process, and, consequently, a geometric factor — changing the sizes of the left atrium. In the formation of left ventricular diastolic dysfunction type 2, the process consistently involves the renin-angiotensin system, namely, renin, a functional factor is presented by the indices of general peripheral vascular resistance and cardiac output, and geometric one includes left atrial diameter and the left ventricular end-diastolic size. Formation of left ventricular diastolic dysfunction type 3 is influenced by such components of the neurohormonal system, as renin and angiotensin-II, then the process subsequently includes peripheral vascular tone and a geometric factor in the form of left atrial diameter and left ventricular end-diastolic size. Thus, in the initial stages of left ventricular diastolic dysfunction in adolescents with myocardial pathology, a significant role is played by the sympathoadrenal system, peripheral vascular tone and left atrial function, and then sequentially the renin-angiotensin system is being involved, which causes an increase in myocardial stiffness and, as a result, the inclusion in the pathological process not only of the left atrium, but also the structure (end-diastolic volume) and function of the left ventricle (stroke volume).

Aim To study the functional condition of sympathoadrenal system as evaluated by beta-adrenoreactivity of erythrocyte membranes (beta-ARM) during two years following renal denervation (RD) in patients with resistant arterial hypertension (RAH) and to determine the relationship of this index with long-term antihypertensive and cardioprotective effectivity of this invasive treatment.Material and methods The study included 48 patients (mean age, 57.2±8.7 years, 18 men) with RAH on a stable antihypertensive therapy. Averaged daily systolic and diastolic blood pressure (SBP and DBP) and levels of beta-ARM were determined at baseline and in 7 days and 2 years following RD. Measurement of beta-ARM was based on beta-adrenoblocker inhibition of erythrocyte hemolysis induced by exposure to hypo-osmotic environment. The beta-adrenoblocker binds to erythrocyte membrane beta-adrenoceptors to prevent the erythrocyte destruction. Increased values of beta-ARM reflect a decrease in the number of functionally active erythrocyte membrane beta-adrenoceptors associated with long-term sympathetic hyperactivity.Results For two years of follow-up, values of average daily BP decreased from 160.4±16.0 / 88.1±14.6 to 145.3±19.3 / 79.4±13.6 mm Hg. At 7 days, the number of beta-ARM had decreased in the group of RD responders (р=0.028) who at two years had decreased their BP by 10 mm Hg or more, while in the group of non-responders, the number of beta-ARM remained unchanged. At one week, beta-ARM values correlated with changes in SBP and DBP (r= –0.54; рConclusion The decrease in beta-ARM content at 7 days after RD shows the procedure efficacy and allows an expectation of clinically significant decreases in BP and LVMM in the long-term after the surgical treatment. At two years after the intervention, the content of beta-ARM increased, and the BP decrease was apparently due to some other mechanisms.

It is widely accepted that sympathetic nervous system plays a crucial role in the development of hypertension. On the other hand, the role of adrenal medulla (the adrenomedullary component of the sympathoadrenal system) in the development and maintenance of high blood pressure in man as well as in experimental models of hypertension is still controversial. Spontaneously hypertensive rats (SHR) are the most widely used animal model of human essential hypertension characterized by sympathetic hyperactivity. However, the persistence of moderately elevated blood pressure in SHR subjected to sympathectomy neonatally as well as the resistance of adult SHR to the treatment by sympatholytic drugs suggests that other factors (including enhanced activity of the adrenomedullary hormonal system) are involved in the pathogenesis of hypertension of SHR. This review describes abnormalities in adrenomedullary hormonal system of SHR rats starting with the hyperactivity of brain centers regulating sympathetic outflow, through the exaggerated activation of sympathoadrenal preganglionic neurons, to the local changes in chromaffin cells of adrenal medulla. All the above alterations might contribute to the enhanced release of epinephrine and/or norepinephrine from adrenal medulla. Special attention is paid to the alterations in the expression of genes involved in catecholamine biosynthesis, storage, release, reuptake, degradation and adrenergic receptors in chromaffin cells of SHR. The contribution of the adrenomedullary hormonal system to the development and maintenance of hypertension as well as its importance during stressful conditions is also discussed.

It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates β3 adrenergic receptor (β3 AR). However, the effect of selective β3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown. We generated a CIH-induced atherosclerosis model through exposing ApoE−/− mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5–21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective β3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected. The expression of β3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE−/− mice in CIH but not in normoxia. Mechanistically, mirabegron activated β3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, β3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects. This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via β3 AR–mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.

Acne vulgaris, a chronic inflammatory skin disease, has been associated with not only sebaceous gland dysfunction but also various endogenous and exogenous stresses. Since sebaceous glands are under neuroendocrine control, including the hypothalamic-pituitary-adrenal axis and neuro-autocrine mechanisms, it remains unclear how psychological stress relates to the pathogenesis of acne. In this study, we investigated the relationship between psychological stress and catecholamine in acne lesions from 18 patients with mild or moderate acne. The State-Trait Anxiety Inventory (STAI) revealed that all patients were anxious, with six having low anxiety and 12 high anxiety. Salivary α-amylase activity (sAA), which is regulated by the sympatho-adrenal medullary (SAM) system, positively correlated with the STAI State Anxiety scores (STAI-S) and was significantly detectable in acne patients with high rather than low anxiety. In addition, the level of normetanephrine, but not metanephrine, both of which are catecholamine metabolites, in hair follicles of acne lesions also positively correlated with the STAI-S. Furthermore, the normetanephrine level was higher in patients with high rather than low anxiety, whereas there was no change in metanephrine in the hair follicles of the acne lesions. Moreover, neither the sAA nor metanephrine and normetanephrine in the acne lesions was related to acne severity in the patients. Thus, these results provide novel evidence that a SAM system-associated increase of normetanephrine level in hair follicles is involved in the acne pathology of patients with anxiety.

Characterization of the progression of cellular states during human embryogenesis can provide insights into the origin of pediatric diseases. We examined the transcriptional states of neural crest- and mesoderm-derived lineages differentiating into adrenal glands, kidneys, endothelium and hematopoietic tissue between post-conception weeks 6 and 14 of human development. Our results reveal transitions connecting the intermediate mesoderm and progenitors of organ primordia, the hematopoietic system and endothelial subtypes. Unexpectedly, by using a combination of single-cell transcriptomics and lineage tracing, we found that intra-adrenal sympathoblasts at that stage are directly derived from nerve-associated Schwann cell precursors, similarly to local chromaffin cells, whereas the majority of extra-adrenal sympathoblasts arise from the migratory neural crest. In humans, this process persists during several weeks of development within the large intra-adrenal ganglia-like structures, which may also serve as reservoirs of originating cells in neuroblastoma.

To study the change in the -adrenergic reactivity of red blood cell membranes in patients during the first year after acute myocardial infarction.The study included 25 patients with acute myocardial infarction (AMI) who signed informed consent to participate in the study. The erythrocyte membrane -adrenoreactivity index (-ARM) was determined in venous blood samples upon admission to the intensive care unit, one day after admission, 6 and 12 months after the index MI was transferred using the BETA-ARM-AGAT reagent kit (Agat-Med, Russia).According to the results of dynamics assessment of -APM during the first day, patients included in the study were divided into 2 groups. Group 1 (n=14) included patients who had an increase in -APM in the first day, and group 2 (n=21) included patients in whom -ARM either did not change or decreased. At the time of admission to the hospital in the formed groups, there were no differences in the -APM index and clinical and anamnestic characteristics. A day after hospitalization, the value of -APM in group 1 significantly exceeded the same indicator in group 2 (p=0.02). At the periods of 6 and 12 months, the -APM indices in the groups did not differ. In the 2nd group of patients, the progression of chronic heart failure to one or more functional classes (NYHA) was significantly more often compared with the 1st group.The study showed that on the first day in patients with AMI, both an increase and a decrease in the activity of the sympathoadrenal system are possible with a further leveling of these differences over the next year. For a group of patients with decreased activity of sympathoadrenal system on the first day, a more unfavorable course of heart failure in the post-infarction period is characteristic.Цель. Изучить изменение показателя -адренореактивности мембран эритроцитов (-АРМ) у пациентов в течение 1-го года после перенесенного острого инфаркта миокарда (ОИМ). Материалы и методы. В исследование включены 25 пациентов с ОИМ, подписавшие информированное согласие об участии в исследовании. Определение показателя -АРМ проводили в образцах венозной крови при поступлении в палату интенсивной терапии, через 1 сут после поступления, через 6 и 12 мес после перенесенного индексного ИМ, с использованием набора реагентов БЕТА-АРМ-АГАТ (ООО Агат-Мед, Россия). Результаты. По результатам оценки динамики показателя -АРМ в течение 1-х суток пациенты, включенные в исследование, разделены на 2 группы. В 1-ю группу (n=14) включены пациенты, у которых в 1-е сутки отмечено увеличение показателя -АРМ, во 2-ю группу (n=21) пациенты, у которых -АРМ либо не изменялась, либо снижалась. На момент поступления в стационар в сформированных группах не выявлено различий по показателю -АРМ и клинико-анамнестическим характеристикам. Спустя 1 сут после госпитализации значение -АРМ в 1-й группе достоверно превышало аналогичный показатель во 2-й группе (р=0,02). На сроках 6 и 12 мес показатели -АРМ в группах не различались. Во 2-й группе пациентов достоверно чаще отмечалось прогрессирование хронической сердечной недостаточности на один и более функциональный класс (NYHA) в сравнении с 1-й группой. Заключение. Проведенное исследование показало, что в 1-е сутки у пациентов с ОИМ возможно как увеличение, так и снижение активности симпатоадреналовой системы с дальнейшим нивелированием этих различий в течение следующего года. Для группы пациентов со сниженной в 1-е сутки активностью симпатоадреналовой системы характерно более неблагоприятное течение хронической сердечной недостаточности в постинфарктном периоде.

The influence of various rhythmic extreme cold effects on the state of autonomic regulation of heart rate in young and aged rats was studied. According to the spectral analysis of heart rate variability, it has been found that in young rats, using rhythmic extreme cold exposures (RECE) temperature regimens of (-120 °С; -120 °С; -120 °С) and (-60 °С; -120 °С; -120 °С) significantly increased adaptive capabilities of the body due to the activation of its own homeostatic regulatory systems. At the same time, the combined regimen of RECE (-60 °С; 120 °С; -120 °С) occurred to be the most optimal for aged animals, since its use was not accompanied with an excessive activation of sympathoadrenal system at the early stages of experimental studies, in contrast to the regimen (120 °С; -120 °С; -120 °С). In addition, the use of this cooling mode contributed to a statistically significant increase in the total power of spectrum of neurohumoral regulation not so much due to a rise in activity of humoral-metabolic regulation link, the prevalence of which is characteristic of an old age, but due to an increase in the tone of vegetative centers, herewith the parasympathetic effects on the myocardium prevailed sympathetic ons.

Unlike noradrenaline, the sympathetic neurotransmitter which overflows to the circulation, adrenaline (ADR) is a secreted hormone, with a low plasma concentration, and plasma concentration for biological action a log order lower than that of noradrenaline. The venous drainage of the left adrenal medulla into the left renal vein does expose this vein to uniquely high plasma ADR concentrations and possible risk of thrombosis at high rates of ADR secretion. There is typically a different timeframe for adrenal medullary and sympathetic nervous system responses: ADR release is short term in contrast with sympathetic activation persisting for years in heart failure and hypertension. The historic view of Walter Cannon, subject to recent review, that the sympathoadrenal system is a unified biological system, was deconstructed further with demonstration of frequent mismatching of adrenal medullary and sympathetic nervous responses. Under gravity stimulation with standing, there is prompt sympathetic activation without ADR release. In many diseases, notably obesity, hypertension, heart failure and depressive illness, an activated sympathetic nervous system and silent adrenal medulla coexist. The therapeutic corollary of this is that ADR blockade is much less commonly needed clinically than pharmacological antagonism of the sympathetic nervous system.

На основании анализа монографий, результатов, опубликованных в физиологических и медицинских журналах, а также представленных на интернет – ресурсах (поисковые системы Google, Pubmed, eLIBRARY, отбор литературных источников по ключевым словам – глюкокортикоиды, гормоны щитовидной железы), установлено, что симпатэктомия (химическая – введение препаратов, тормозящих передачу возбуждения в синапсах симпатической нервной системы, например, гуанетидина, 6-гидроксидофамина, резерпина и др.; хирургическая – удаление симпатических ганглиев; иммунная – введение антител к фактору роста нервов) снижает резистентность организма к стрессу, поскольку значительно ослабляет ответ гипоталамо-гипофизарно-надпочечниковой и симпатоадреналовой систем, делая невозможной реализацию адаптивных эффектов гормонов их эффекторного звена в этих условиях. Установлены следующие механизмы снижения стрессоустойчивости при блокаде передачи возбуждения в адренергических синапсах: интенсификация перекисного окисления липидов и протеолиза; нарушения белкового и углеводного обмена, вызывающие появление дистрофических изменений в различных тканях; нарушение функции сердца, которое обеспечивает деятельность всех систем, осуществляющих адаптацию к стрессорным воздействиям.

It is essential to understand responses to stress and the impact of stress on physiological and behavioural functioning of hens, so as to assess their welfare. The current understanding of stress in laying hens is comprehensively reviewed here. Most research on stress in hens has focussed on the activity of the adrenal glands, with the most common approach being to measure corticosterone, which is the predominant glucocorticoid produced by birds in response to stress. While these measures are useful, there is a need to understand how the brain regulates stress responses in hens. A greater understanding of the sympathoadrenal system and its interaction with the hypothalamo–pituitary–adrenal axis is required. There is also a lack of knowledge about the many other peptides and regulatory systems involved in stress responses in hens. The usefulness of understanding stress in hens in terms of assessing welfare depends on appreciating that different stressors elicit different responses and that there are often differences in responses to, and impacts of, acute and chronic stress. It is also important to establish the actions and fate of stress hormones within target tissues. It is the consequences of these actions that are important to welfare. A range of other measures has been used to assess stress in hens, including a ratio of heterophils to lymphocytes and haematocrit : packed cell-volume ratio and measures of corticosterone or its metabolites in eggs, excreta, feathers and the secretions of the uropygial gland. Measures in eggs have proffered varying results while measures in feathers may be useful to assess chronic stress. There are various studies in laying hens to indicate impacts of stress on the immune system, health, metabolism, appetite, and the quality of egg production, but, generally, these are limited, variable and are influenced by the management system, environment, genetic selection, type of stressor and whether or not the birds are subjected to acute or chronic stress. Further research to understand the regulation of stress responses and the impact of stress on normal functioning of hens will provide important advances in the assessment of stress and, in turn, the assessment of welfare of laying hens.

FMF is an autoinflammatory disease characterized by recurrent attacks and increased IL-1 synthesis owing to activation of the pyrin inflammasome. Although knowledge of the mechanisms leading to the activation of pyrin inflammasome is increasing, it is still unknown why the disease is characterized by attack. The emergence of FMF attacks after emotional stress and the induction of attacks with metaraminol in previous decades suggested that stress-induced sympathoadrenal system activation might play a role in inflammasome activation and triggering attacks. In this review, we will review the possible molecular mechanism of stress mediators on the inflammation pathway and inflammasome activation. Studies on stress mediators and their impact on inflammation pathways will provide a better understanding of stress-related exacerbation mechanisms in both autoinflammatory and autoimmune diseases. This review provides a new perspective on this subject and will contribute to new studies.

Introduction. The carotid body is a chemoreceptor organ and the initial link of the reflex regulation of car-diovascular and respiratory systems. However, molecular genetic and immunohistochemical characteristics of the human carotid body remains underinvestigated. Although there are numerous studies of the second half of the 20th century devoted to the classical light-optical histology of the human organ, the immunohis-tochemical investigations are very few. The aim of our study was to clarify immunohistochemical features of the human carotid body in comparison with those of the most commonly used laboratory animals. Materials and methods. The study was performed on 10 carotid bodies of the adult human of different ages of both sexes using immunoperoxidase labeling with antibodies to bIII-tubulin, tyrosine hydroxylase, syn-aptophysin, PGP9.5, neurofilaments 200kDa, S100, and GFAP. Results. Nerve fibers passing between the lobules, as well as entering them, were positive for bIII-tubulin, tyrosine hydroxylase, PGP9.5 and neurofilaments. Type I cells had cytoplasmic reaction for bIII-tubulin and synaptophysin as well as cytoplasmic and nuclear staining for PGP9.5. At the same time, they had weaker reaction for tyrosine hydroxylase. Type II cells were positive for GFAP and S100. Conclusion. Immunohistochemical characteristics of the human carotid body were similar to those of rats and mice. The human carotid body cells and nerve fibers showed the same distribution of PGP9.5, bIII-tubulin, synaptophysin, neurofilaments, GFAP and S100 as rat and mouse carotid body cells. However, human carotid body reaction for tyrosine hydroxylase was much lower, which may indicate a smaller amount of synthesized catecholamines compared to the carotid body in rats and mice. Keywords: human carotid body, immunohistochemistry, sympathoadrenal system, tyrosine hydroxylase

During the development of the acute phase of ischemic stroke (IS), the cytoplasmic membranes of cells and receptor complex are primarily damaged. Structural changes in brain tissue are accompanied by violations of its electric physical characteristics, which are quite qualitatively possible to record using microwave dielectrometry. The aim of the studywas to learn the features of changes in the dielectric properties of peripheral blood erythrocytes of patients with IS during in vitro exposure to adrenergic drugs depending on the severity of the disease to optimize diagnosis. Material and methods of research.Measurements of complex dielectric constant (CDC) were performed by EHF dielectrometry at a fixed frequency of 39.5 × 109Hz, which is in the region of γ-dispersion. The work was based on the materials of a comprehensive examination of 350 patients with the first in the life of IS on the 1st, 10th and 21st day of the disease. The severity of the condition and the degree of neurological deficit were determined using the stroke scale of the US National Institutes of Health (NIHSS) in the first hours of the disease, in the dynamics of treatment on the 10th and 21st day. There were 2 clinical groups: 1st (n = 183) – patients in a state of moderate severity (mean score on the NIHSS scale 11.74±0.33); 2nd (n = 167) – patients with severe IS (average score on the NIHSS scale 24.06±0.29). Results.In the control group, there was a significant decrease after exposure to adrenaline solution. The reaction to adrenaline in patients with IS was almost absent. It indicates a decreasing of erythrocytes β-adrenoceptors (β-ARs) sensitivity to stimulants due to their desensitisation. In patients with moderate severity, erythrocytes are more reactive than in patients with more severe IS. Conclusions.The deviation of CDC of erythrocytes induced by adrenergic drugs in vitro is a manifestation of a specific response of cells to biologically active substances and depends on the functional state of the sympathoadrenal system

A variety of factors influence the performance of schoolchildren. The main factors are psycho-emotional stress and systematic physical activity that requires a constant tension of body's regulatory systems aimed at mobilizing the functional body reserves. The analysis of blood pressure enables to estimate quantitative and qualitative changes in the regulation of the cardiovascular system. The combination of the Stroop test and the monitoring of the cardiovascular system make it possible to assess not only attention and cognitive function parameters, but the phases of the stress response of regulatory systems as well. The purpose of the study was to analyze the relationship between stress factor and the functional state of adolescent cardiovascular system. In the context of stress factor (Stroop test), the circulatory system of students gets activated, and its indicators vary differently among boys and girls. At rest, girls have the lowest performance of the circulatory system. Before the test, heart rates vary in boys and girls in different ways. In the course of our study, we have found out a direct relationship between heart rate, blood pressure before and after psycho-emotional load that testifies the predominance of the sympathoadrenal system activity. We have revealed the arterial hypertension is determined by physiological and social factors. Prevention of arterial hypertension in existing standards of schools requires reconsidering and improving of educational approaches, especially in terms of physical education.

The key role in the pathogenesis of cardiovascular diseases is played by sympathetic overdrive - chronic hyperactivation of the sympathoadrenal system, which ultimately leads to its depletion. Heart rate, blood pressure, and plasma renin levels are markers of hypersympathicotonia. In large-scale clinical studies, it was proved that an increased resting heart rate is an independent risk factor for cardiovascular diseases and is associated with an increased risk of death, and the most effective treatment strategy is to prescribe beta-blockers that affect all parts of the sympathetic overdrive, exhibiting additional metabolic effects.

From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.

The stress response is a preserved evolutionary response that functions to enhance the survival of the species. In mammals, the stress response is characterized by activation of the HPA axis and sympathoadrenal system (SAS) as well as the increased synthesis and secretion of vitamin C. Cortisol, catecholamines, and vitamin C act synergistically to increase hemodynamic reserve, maintain immune function and protect the host against excessive oxidant injury. Humans (and anthropoid apes) have lost the ability to synthesize vitamin C and therefore have an impaired stress response. The inability to produce vitamin C has serious implications in septic humans. Treatment with vitamin C appears to restore the stress response and improve the survival of stressed humans.

Introduction. The cells in adrenal medulla, carotid body and the organ of Zuckerkandl have the common origin from the neural crest. Nevertheless, despite the similarity in both histological and biochemical characteristics of these organs, contemporary scientific paradigm contrasts the carotid body with the adrenal gland and the organ of Zuckerkandl. The adrenal gland and the organ of Zuckerkandl are considered to function as endocrine glands whereas carotid body is thought to be a chemoreceptor organ. The endocrine function of the carotid body is still in question. The aim of the work was to evaluate the possibility of the presence of endocrine function by the carotid body in the embryonic, prefetal and early fetal period of human development by immunohistochemistry and compare it with the function of the organ of Zuckerkandl and the adrenal medulla. Materials and methods. The study was performed on 5 fetal autopsies (gestational age 8–20 weeks) using immunoperoxidase labeling with antibodies to bIII-tubulin, tyrosine hydroxylase, synaptophysin and PGP9.5. Results. In all samples of the carotid body, the organ of Zuckerkandl and the adrenal medulla, the cells showed a positive reaction to all the markers. All carotid bodies showed very high TH/bIII ratio approaching unity. The organ of Zuckerkandl in all fetus showed much higher TH/bIII ratio than that inthe carotid body. In the adrenal glands at 11–20 weeks of gestation TH/bIII ratio was even greater. In the adrenal gland in 8-week embryo this ratio was lower than in the carotid body. Conclusion. We have showed that the number of TH-positive cells in the carotid body in the embryonic and early fetal periods is much higher than in postnatal period. Our data may indicate endocrine function of the carotid body during the antenatal period of development. Thus, the carotid body is likely to synthesize catecholamines while the adrenal medulla is functionally immature and cannot support the body’s homeostasis. Keywords: sympathoadrenal system, human development, carotid body, organ of Zuckerkandl, adrenal gland.

Recently the B6.CBA-D13Mit76C (B6-M76C) and B6.CBA-D13Mit76B (B6-M76B) recombinant mouse lines have been created, which differ in the sensitivity of the 5-HT1A-receptor to chronic activation by an 8-OH-DPAT (8-hydroxy-2- (di-n-propylamino) tetralin). 5-HT1A-receptor is the key regulator of the brain serotonin (5-HT) system that is implicated in the regulation of stress response. In this work, it was found that acute emotional stress (immobilization of 40 min) increases the expression of the c-fos gene, which is a marker of the response to stress, in the brain of both lines. The stress-induced increase c-fos expression in the striatum, hypothalamus, and cortex of B6-M76C mice was more pronounced. The reaction to emotional stress led to an increase in the ratio of the serotonin metabolite - 5-HIAA (5-hydroxyinodolacetic acid) to 5-HT in the midbrain and hippocampus in both lines. An increased 5-HIAA/5-HT ratio was detected in the hypothalamus B6-M76C and cortex B6-M76B of mice after stress. Moreover, the reaction to stress led to decrease in the level of norepinephrine in the hippocampus and hypothalamus in B6-M76C mice. The levels of dopamine, norepinephrine, epinephrine and the dopamine/norepinephrine ratio in the adrenal glands increased in response to the stress effect only in B6-M76C. The present study showed that the sympathoadrenal system is more sensitive to acute stress in the B6-M76C mice. Reaction to stress in B6-M76C mice leads to an increase in the content of norepinephrine and epinephrine in adrenal tissue. An increase in the adrenal dopamine/norepinephrine ratio may indicate a more rapid transition of catecholamine biosynthesis intermediates (dopamine) to norepinephrine and further epinephrine due to the acceleration of the biosynthetic process in response to stress in B6-M76C mice. In addition, an increased sensitivity of the hypothalamic neurons to the action of stress in B6-M76C was shown. Thus, B6-M76C mice are of significant interest for the study of the hypothalamic-pituitary-adrenal system with an overactive response to stress, and can contribute to the identification of new biomarkers for clinical studies

In recent years, the “non-autonomous motor neuron death” hypothesis has become more consolidated behind amyotrophic lateral sclerosis (ALS). It postulates that cells other than motor neurons participate in the pathology. In fact, the involvement of the autonomic nervous system is fundamental since patients die of sudden death when they become unable to compensate for cardiorespiratory arrest. Mitochondria are thought to play a fundamental role in the physiopathology of ALS, as they are compromised in multiple ALS models in different cell types, and it also occurs in other neurodegenerative diseases. Our study aimed to uncover mitochondrial alterations in the sympathoadrenal system of a mouse model of ALS, from a structural, bioenergetic and functional perspective during disease instauration. We studied the adrenal chromaffin cell from mutant SOD1G93A mouse at pre-symptomatic and symptomatic stages. The mitochondrial accumulation of the mutated SOD1G93A protein and the down-regulation of optic atrophy protein-1 (OPA1) provoke mitochondrial ultrastructure alterations prior to the onset of clinical symptoms. These changes affect mitochondrial fusion dynamics, triggering mitochondrial maturation impairment and cristae swelling, with increased size of cristae junctions. The functional consequences are a loss of mitochondrial membrane potential and changes in the bioenergetics profile, with reduced maximal respiration and spare respiratory capacity of mitochondria, as well as enhanced production of reactive oxygen species. This study identifies mitochondrial dynamics regulator OPA1 as an interesting therapeutic target in ALS. Additionally, our findings in the adrenal medulla gland from presymptomatic stages highlight the relevance of sympathetic impairment in this disease. Specifically, we show new SOD1G93A toxicity pathways affecting cellular energy metabolism in non-motor neurons, which offer a possible link between cell specific metabolic phenotype and the progression of ALS.

A comprehensive study of the functional state of the sympathoadrenal system (SAS) and adrenal cortex (AC) in boys aged of 11-15 years, was carried out depending on their age, puberty stage and academic year period, on the basis of indices of the daily adrenaline (A), noradrenaline (NA), 17-ketosteroids (17-KS) and 17-oxyketosteroids (17-OKS) excretion. A certain synchronism of the manifestation offunctional activity of the SAS mediator level, glucocorticoid and androgen AC function is determined as boys grow older and during their pubertal changes. At the same time the different dynamics of the studied indices in boys aged of from 14 to 15 years and by the V puberty stage is marked. During the academic year changes of hormone and hormonal metabolite excretion, having a different focus and intensity in the age groups were observed: a significant decrease of age NA excretion and androgen metabolite indices (at 15) of 14 and 15 year-old teenagers at the end of the academic year is found out, against the backdrop of a substantial and long-term increase of glucocorticoids (February, April), with their dangerous catabolic effect on a child’s body and their depressing effect on the immune response.