In experiments on segments of the rat superior mesenteric artery (SMA) under isometric conditions, the effect of cold on the reactivity of this artery, estimated by the magnitude of the contractile reaction of its segments to noradrenaline (NA) at a concentration of 0.01–10.0 µM, as well as to electrical field stimulation (EFS) of perivascular nerves with a frequency of 3, 10 and 40 Hz in the absence and presence of NA in the medium and at a temperature of 37 oC or 25 oC was studied. Cooling was found not to change the tone of the SMA caused by NA at all the concentrations used. In the absence and presence of NA at a low concentration (0.01–0.10 µM), cooling leads to a significant decrease in the neurogenic response of the SMA at all frequencies of EFS, while in the presence of NA at a high concentration (1–10 µM), cooling has no statistically significant effect on this response. In the presence of NA at a low concentration, cooling at low EFS frequencies insignificantly, and at high frequency significantly reduces the potentiating effect of NA on neurogenic contraction of SMA. NA at a high concentration under normal temperature conditions, reduces the neurogenic contraction at all EFS frequencies, while under cooling conditions at low frequencies it has a potentiating effect, and at high EFS frequency it has a depressing effect. The results obtained show that the depressing effect of cold on the neurogenic constriction of the rat SMA, observed at low and disappearing at high concentrations of NA, as well as on the NA-evoked potentiation of the neurogenic vasoconstriction, is not associated with a decrease in the contractile effect of NA, which is the main neurotransmitter in this artery. These effects can contribute to the redistribution of blood from the surface deep into the body, thus reducing heat loss and improve thermoregulation.
Progesterone plays a key role in reproductive processes in the female body and has effects in the central nervous system and other tissues. Progestins are widely used clinically in contraception and hormonal therapy. The classical effects of progesterone are mediated through nuclear receptors, which are ligand-dependent transcription factors. Since 2003, membrane progesterone receptors (mPRs) of the adiponectin receptor family of five subtypes have been in the spotlight. Their role in many normal and pathological processes in the body remains unclear. Determining the mechanisms of action of progesterone is complicated by the fact that activation of different types of receptors can cause opposite effects. The search for selective ligands of mPRs is an important task, since the use of such compounds makes it possible to differentiate the effects of progestins mediated by different types of receptors. The review analyzes the action of three selective ligands of mPRs, described and studied at present. One of them is widely used in international research, the other two have been identified and used in our work. The advantages and defects of these three compounds and the studies of mPRs functions conducted using them are considered. In conclusion, the prospects for creating new selective mPRs ligands are assessed, taking into account the structural features of their ligand-binding pocket. We found that the 3-keto group of progesterone and its derivatives, which is fundamentally required for binding to nuclear steroid receptors, is not important for interaction with mPRs. Our conclusion was confirmed in a study published in 2022 using modeling techniques and mutational analysis. It is this structural feature that will further serve as the basis for the development of the synthesis of compounds that are effective and selectively interact with mPRs.
Aerobic exercise training is aimed to prevent and correct various cardiovascular disorders. To study its effects, various rodent models are currently in use, among which the rat model of voluntary wheel running is of particular interest, as its pattern of motor activity is close to natural rat locomotion, while being non-stressful. This work was aimed at a comprehensive investigation of wheel running effects on the neural control of heart rate (HR) in rats. The animals, aged 6 weeks, were divided into two groups: training (TR, free access to wheels, n = 11) and sedentary control (CON, n = 12). After a 6-week training, ECG was recorded in freely moving rats using skin electrodes in three modes: at rest, after autonomic blockade of cardiotropic influences, and during 4-min air-jet stress. Autonomic neural influences were analyzed by administering the β1-adrenoceptor blocker atenolol (2 mg/kg) and the peripheral M-cholinoceptor antagonist methylatropine (1 mg/kg), as well as by analyzing HR variability via spectral and wavelet analyses. At rest, the TR group showed a decrease in the baseline HR level vs. CON group. Аtenolol decreased HR equally in two groups, but methylatropine elicited a more significant increase in HR in the TR vs. CON group. After atenolol and methylatropine co-administration, HR levels in two groups were similar. TR rats showed an increased contribution of high-frequency (0.75–3 Hz) oscillations to the total RR interval power spectrum. During emotional (air-jet) stress, the TR group demonstrated a more pronounced increase in HR vs. CON group. In addition, stressed TR rats exhibited a decrease in the amplitude of HR high-frequency oscillations, which was absent in the CON group. Thus, voluntary wheel running in rats is accompanied by an increase in parasympathetic influences on the heart, as manifested in an increase both in respiratory sinus arrhythmia and in vagal effects on the resting HR level (increased tachycardia). Moderate resting bradycardia promotes a more pronounced increase in HR under emotional stress conditions due to suppression of parasympathetic cardiac influences.
Pulmonary arterial hypertension (PAH) is characterized by an increase of a pressure in the pulmonary circulation; PAH is accompanied by activation of the sympathetic (SNS) and the renin-angiotensin-aldosterone system (RAAS). However, PAH-associated changes in baroreceptor regulation of systemic circulation, which is tightly interwoven with SNS and RAAS, have not been studied. The baroreceptor response (BRR) was studied in a chronic monocrotaline (MCT) model of PAH in rats (Wistar, 290 ± 30 g, 2–4 months). Phenylephrine as an agonist of α1-adrenergic receptor and sodium nitroprusside as NO donor were gradually administered to chronically catheterized, non-anesthetized control animals and animals with PAH (4 weeks after MCT administration) to induce vasomotor responses. Mean arterial pressure and heart rate (HR) were recorded under the action of vasoactive compounds alone or under the action of vasoactive compounds in presence of angiotensin-II (ATII), atropine. The parameters characterizing baroreceptor change in HR including maximal and minimal heart rate (HRmax, HRmin), reflex tachycardia (TBRR) and bradycardia (BBRR), range (ABBR) and the baroreceptor response sensitivity index (SIBRR) were calculated. A significant decrease in HRmax, TBRR, ABBR (but not BBRR), as well as the sensitivity index of BRR was observed in rats with PAH. ATII induces significant and different changes in the BRR parameters in control rats and in rats with PAH if administered 4 weeks after the start of the experiment. In rats with PAH, ATII causes less pronounced changes in HRmax, TBRR, and BBRR than in control animals. ATII insignificantly affects parasympathetic component of the baroreceptor reflex in rats with PAH. Thus, at least in the MCT-mediated model in rats, PAH significantly deteriorates the baroreceptor regulation of HR. This effect manifests in a decrease in the range and sensitivity of the baroreceptor response. Also, PAH unequally affects the sympathetic and parasympathetic control of the baroreceptor regulation of HR. On the other hand, ATII exhibits weak ability to alter BRR in rats with HAP. In conclusion, PAH leads to a disfunction of immediate, reflex mechanisms HR and systemic circulation control.
Diabetes mellitus (DM), along with ischemia, is one of the top ten causes of death in the globalpopulation, according to the latest World Health Organization (WHO) data. Clinical research data have revealed a high risk of stroke and heart attacks in patients with diabetes. However, there is still a lack of understanding of the involvement of pannexin 1 (Panx1) protein in cerebral ischemia combined with DM. In the presented study, we used the Panx1 gene knockout mice in models of streptozotocin-induced diabetes and photoinduced ischemia to investigate the effect of the Panx1 on the severity of ischemic brain damage and systemic inflammation in mice with a combination of cerebral ischemia and diabetes. It has been found that under conditions of experimental diabetes, the knockout of the Panx1 gene significantly reduces the size of the ischemic lesion, stabilizes the ischemia-induced increase in the blood-brain barrier permeability, reduces the number of errors in the sensorimotor test and the level of neutrophils in the blood. It is important to note that the Panx1 knockout exhibits a protective effect only in the presence of diabetes mellitus, without significantly affecting the severity of ischemic brain injury in mice without streptozotocin-induced diabetes. Panx1 knockout also did not affect the severity of hyperglycemia in animals in this diabetes model. It can be assumed that the efficacy of the treatment for pathologies combined with diabetes mellitus can be enhanced by incorporating pannexin channel blockers into the complex therapy, representing a novel approach to addressing these serious conditions.
Since the last century, it has been known that inert gases can cause a range of physiological effects. The biological activity of inert gases is an extremely multifaceted phenomenon. Despite the similarity of most physical and chemical characteristics, they differently influence many organs and tissues by interacting with a variety of protein targets. Xenon, krypton, and argon are now known to be capable of altering the functional state of the central nervous system and correcting some psychoemotional disorders. In addition, noble gases act on the processes of apoptosis and cellular stress response, affect the immune status and various homeostatic parameters. The cytoprotective effects of helium on the cardiovascular and respiratory systems have also been convincingly demonstrated. Thus, inert gases are currently being considered as potential tools to correct various diseases. This review analyzes literature data on the physiological effects of inert gases, as identified in biomedical studies on patients, as well as in cell culture and in vivo models. Each chapter is dedicated to a particular gas of this group, starting from the most studied. For each of the inert gases (helium, neon, argon, krypton, xenon, and radon), the physiological activity, possibility of being used in medicine, and some known mechanisms of its action are considered. Moreover, the existing data are critically analyzed, and the key gaps to be filled in future research are highlighted.
Liver diseases accompanied by obstructive cholestasis (OC) often depend on sex. Prolactin hormone levels are often elevated in a variety of hepatopancreatobiliary zone diseases, which is an adverse prognostic sign. To clarify the role of prolactin in the development of pancreatitis under OC conditions, structural changes in hepatic and pancreatic tissue female rats against the background of hyperprolactinemia were investigated. The rats were divided into the following experimental groups: group K—control animals; group HyperPrl—animals with normal hepatic function against the background of hyperprolactinemia; group BP—animals with biliary pancreatitis under OC; group BPhyperPrl—animals with biliary pancreatitis under OC against the background of hyperprolactinemia. Hyperprolactinemia was modeled by transplanting the donor’s pituitary gland under the recipient’s kidney capsule. Biliary pancreatitis was simulated with a ligation of the biliopancreatic duct 1 cm prior to its discharge into the duodenum, causing obstruction of the ducts of the splenic segment of pancreas. After 14 days of operations, a biomaterial was collected. The biochemical indicators of the blood serum confirmed the development of OC and pancreatitis. The structure of the pancreatic parenchyma in the BP and BPhyperPrl groups was changed, especially in the splenic segment. In both groups, tubulo-insula and tubulo-acinar complexes, inflammatory infiltration, acinaro-ductal metaplasia were found, which was accompanied by severe pancreatic parenchyma fibrosis in the group BPhyperPrl. It is important to note that the duodenal segment of pancreas continued to compensate for pancreatitis development in the BP and BPhyperPrl groups. In the hepatic tissue, histological confirmation of the development of obstructive cholestasis was shown in the BP and BPhyperPrl groups, with the loss of the beam structure of hepatocytes and the development of pericellular fibrosis against the background of hyperprolactinemia. Thus, we first showed in our work that female rats with increased prolactin concentration on the background of OC develop a heavier form of pancreatitis with a pronounced pancreatic fibrosis. This model of the development of biliary pancreatitis under OC can be used not only to study the role of prolactin in disruption of the pancreas, but also its participation in compensatory reactions to maintain the work of the exocrine part of the pancreas in this pathology.
Using fluorescence microscopy, we studied the participation of Ca2+-acceptor proteins in the processes of the exo-endocytotic cycle of neurotransmitter quantal secretion in the neuromuscular junction of the somatic muscle of the earthworm Lumbricus terrestris. Inhibition of calcineurin, calmodulin and Ca2+/calmodulin dependent protein kinases led to an increase in the process of endocytosis. Blocking the phosphorylation of synaptic proteins enhances the process of endocytosis, causes an increase in the size of the total vesicular pool and accelerates the turnover of synaptic vesicles. It can be concluded that calcium modulation of vesicle exo-endocytosis at the synapses of the evolutionarily primary somatic muscles of annelids occurs with the participation of calcineurin, calmodulin and Ca2+/calmodulin-dependent protein kinases.
The work examined the expression of apoptosis, autophagy and necroptosis markers in hippocampal cells of rats after long-term consumption of excessive F- doses at the transcriptional and translational levels. Male Wistar rats were divided into 4 groups receiving 0.4 (control), 5, 20 and 50 mg/l F- (as NaF) for 12 months. The changes in contents of effectors of mitochondrial (Bcl-2, Bax, Caspase-9, Caspase-3) and receptor (Caspase-8, Fas) pathways of apoptosis, mediators (Ulk-1, Beclin-1) and modulators (AMPK, Ark, mTOR) of autophagy, as well as that of necroptosis (RIP and MLKL) were assessed by immunoblotting, the gene expression (Bcl2, Bax, Casp3, Ulk1, Beclin1, Prkaa1, Akt, and mTor) – by real-time PCR. In the hippocampus of F – exposed animals, the expression ratio of Bcl2/Bax genes and Bcl-2/Bax proteins decreased, caspase-9 and caspase-3 were activated, but the level of caspase-8 and membrane Fas receptor remained stable. Long-term F- consumption had no effect on the content of autophagy initiator Ulk-1 and protein kinases AMPK, Akt and mTOR, but resulted in inhibition of key autophagy mediator Beclin-1. The expression level of necroptosis RIP and MLKL effectors in the hippocampal cells of rats received excessive F- did not change as well. Thus, long-term F- exposure was accompanied by activation of apoptosis, mainly through the mitochondrial pathway, at the background of autophagy suppression.
The prefrontal cortex (PFC) plays a key role in cognitive plasticity and is involved in various processes of higher nervous activity. At the same time, studying the processes underlying various forms of behavior in which PFC neurons participate is a non-trivial task. The associative functions of the PFC are associated with the nature of the connectivity of this structure with other areas of the brain, which, according to recent data, is much more complex than previously thought. Thus, it becomes clear that the axons of PFC projection neurons have many collaterals projecting to many different targets in the brain. In this review, we highlight the latest results in studying the connectivity of PFC neurons using the latest methods for analyzing projections and single-cell transcriptomes. Brain-derived neurotrophic factor (BDNF) plays an important role in the functioning of these neurons and their projection targets, but the transport of this neurotrophin by PFC projection neurons to structures where it is not locally expressed may be especially important. We review recent results mapping such neurons in the PFC, highlighting Bdnf expression and potential role in the pathogenesis of mental disorders.
The study of peripheral nervous system glial cells is an actual problem of modern neurobiology. The purpose of this work was to summarize our own and published data on the distribution of glial fibrillary acidic protein (GFAP) in peripheral nervous system (PNS) glial cells. The features of GFAP expression in glial cells of the enteric nervous system, dorsal root ganglion and peripheral nerve were examined. A comparative study of different populations of PNS gliocytes led to the conclusion that the intermediate filament protein GFAP is distributed differently in them. Analysis of the literature showed that despite the fact that this protein is widely used as a molecular marker of glial activation, there is still no understanding of the exact mechanisms of GFAP participation in the glial reactive response. The described features of GFAP+gliocytes from different parts of the PNS demonstrate the functional polymorphism of this protein. Its ability to be expressed in peripheral nervous system gliocytes in response to injury requires further research.
The electromyographic activity of the soleus muscle is a reliable indicator of its functional status. Unloading of support causes an immediate cessation of electrical activity in the soleus muscle, which resumes upon restoration of the support load. Prolonged support unloading, however, results in the emergence of spontaneous electrical activity in the soleus muscle. Previous research has established a correlation between this activity and the presence of the potassium-chloride cotransporter (KCC2) on the membranes of spinal cord motor neurons. Additionally, it has been demonstrated that the introduction of the KCC2 activator prochlorperazine can eliminate spontaneous muscle activity. This study aimed to investigate the impact of CLP290, an alternative KCC2 activator, on the spontaneous tonic activity of the rat soleus muscle. The results indicated that daily administration of CLP290 to rats during a 14-day period of hindlimb suspension prevented the reduction in KCC2 levels in the motor neurons of the lumbar spinal cord and the increase in spontaneous tonic activity in the soleus muscle. Notably, there were no significant differences in the cross-sectional area of slow-type fibers between the antiorthostatic suspension groups with and without CLP290 administration.
IP3 receptors are found in significant quantities in muscle fibers in the sarcoplasmic reticulum, nucleus and mitochondria. We hypothesized that activation of IP3 receptors (IP3Rs) during muscle unloading may induce a weak calcium release signal, both cytosolic and nucleoplasmic, that promotes (possibly with other signaling cascades) the activation of transcription factors, leading to the expression or repression of genes involved in muscle phenotype. This hypothesis was tested by blocking IP3R during unloading of rat muscles by administering 2-APB (2-aminoethoxydiphenyl borate). Wistar rats were administered intraperitoneally at a dose of 10 mg/mg in 5 % DMSO daily. We found that the IP3R state influences the development of atrophic processes in the postural m. soleus during unloading. Administration of the IP3R blocker 2-APB to animals successfully prevented a decrease in m. soleus cross-sectional area (CSA) of both fast and slow muscle fibers. The slowdown in CSA decrease upon administration IP3R inhibitor during 7 days m. soleus unloading is associated with the prevention of a decrease in ribosomal biogenesis and an increase in the expression of autophagy markers ULK-1 and IL-6.
In experiments on 3-day-old rats to identify the possible involvement of adrenoreceptors (AR) in the development of pathologic heart rhythm with high-amplitude (> 0.5 s) bradycardic complexes (PHRBC) occurring in newborn rats after NiCl2 administration, a comparative analysis of changes in heart rate variability (HRV), heart rate, and respiration after injection of nickel chloride and a high dose of the β-AR agonist isoproterenol was carried out. Injection of NiCl2, which blocks T-type voltage-dependent Ca2+ channels (T-VDCC), causes in 100 of rats the occurrence of PHRBC accompanied by a decrease in the role of neural influences and an increase in the role of neurohumoral factors in the mechanisms of heart rate regulation. Activation of β-AR causes shifts of physiological parameters qualitatively and quantitatively similar to those observed after NiCl2 poisoning in rats, but PHRBC does not occur. Pharmacological analysis with premedication of rats with β-AR antagonists (propranolol, atenolol) or α-AR antagonists (phentolamine) followed by NiCl2 administration showed that β-AR blockade with the nonselective adrenolytic propranolol prevents the development of PSRBC in half of the rats. In animals with pathologic arrhythmia occurring after NiCl2 injection, a rapid increase in the load on the sympathoadrenal system is noted, and the initial (background) instability of the mechanisms of heart rhythm regulation is revealed. Blockade of α- and β1-AR does not prevent the development of PHRBC during subsequent NiCl2 administration, which suggests the participation of β2-AR in the development of arrhythmia. Administration of the selective β2-AR agonist clenbuterol to rats leads to a decrease in HRV, including neurohumoral regulation and the appearance of low-amplitude (< 0.1 s) bradycardic complexes (BC) in 22 of rats. The results obtained by us together with the analysis of the literature suggest that β-AR plays an important role in the complex changes in the balance of regulatory influences in the occurrence of PHRBCs. Activation of β1-AR contributes to increased release of catecholamines by adrenal chromaffin cells, increased role of neurohumoral component of heart rhythm regulation and causes activation of β2-AR. Blockade of β2-AR, on the contrary, reduces the release of catecholamines and prevents the development of pathological arrhythmia. The second necessary factor leading to the development of arrhythmias with high-amplitude BCs is blockade of T-type calcium channels.
In this review, we address the oligomerization of G protein-coupled receptors (GPCRs), which significantly expands the functional capabilities of cells in living organisms by modulating intracellular signaling pathways. This provides a variety of physiological effects in both normal and pathological states. The structure and intracerebral localization of one of the most studied heterodimers, the D1-D2 receptor complex, and its signaling cascades, which correlate with the development of depressive disorders, are considered. Sex differences in the functioning of this heterodimer are analyzed, and the issue of the selectivity of bivalent synthetic ligands in triggering specific intracellular pathways is discussed, highlighting their potential as therapeutic targets for the targeted treatment of depressive disorders. The concluding part of the review is dedicated to the diversity of dopamine receptor heterodimers with other members of the GPCR family and their role in the pathophysiology of depression.
Spinal cord injury (SCI) is manifested by pathologic changes in the areas significantly distant from the area of primary injury. In order to find new potential therapeutic targets to restore motor function, it is particularly relevant to identify the causes and mechanisms of these shifts in the lumbar spinal cord when injury occurs in the proximal spinal cord. On the rat model of dosed SCI at the Th8 segment level the expression of Ca-binding protein parvalbumin (PARV), osteopontin (OPN), and glypican 4 (GPC4) in neurons of laminae VII, VIII and IX within segments L3-4 on 7 and 60 days of the experiment was studied. Laminas VII and IX show a decrease in the number of PARV+ neurons during the acute and chronic phase of SCI, which may indicate a decrease in calcium binding in ventral horn neurons at the level of segments L3-4. Decreased PARV expression in these neurons indicates an increased risk of their vulnerability and impaired motor function. The pattern of OPN expression in lumbar horn neurons distant from the epicenter of traumatic injury was studied for the first time. In all the studied laminae in the ventral horns of the gray matter, we did not observe shifts in the number of OPN+ neurons both in the acute and chronic phases of SCI. In lamina IX of the lumbar spinal cord, we found an increase in the number of GPC4+ neurons in the acute posttraumatic period, which can be regarded as a key positive adaptive reaction of neurons in the lumbar spinal cord remote from the epicenter of injury. The assessment of this reaction as positive is based on the data on the binding of GPC4 anchored on the neuron surface to various molecules with neuroprotective activity and stimulating neuroregeneration.
Intrauterine growth restriction (IUGR) is one of the most common pathologies of pregnancy. Due to this pathology, the functioning of many systems, including the cardiovascular, is impaired. In adult animals, who have suffered IUGR, the contribution of procontractile mechanisms of vascular tone regulation (e.g., Rho-kinase signaling pathway) increases, while that of anticontractile mechanisms (e.g., endothelial NO), on the contrary, decreases, which can lead to vasospasm and impaired blood supply to the organs. Since NO and Rho-kinase play a pronounced vasomotor role in early postnatal ontogenesis, this work was aimed to assess the effect of IUGR on the contribution of these mechanisms to the regulation of arterial contractile responses during the early postnatal period in rats. IUGR was modeled by restricting the amount of food calories consumed by females (by 50 11 of pregnancy until parturition. In rat offspring aged 11–12 days, we studied the responses of the isolated saphenous artery in isometric mode and evaluated the content of mRNA and proteins of interest in this artery. IUGR did not alter the offspring arterial reactivity to the α1-adrenergic receptor agonist methoxamine. The increase in vasocontractile responses to methoxamine in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor L-NNA, as well as the expression levels of eNOS (mRNA and protein) and arginase-2 (mRNA), did not change in the arteries of IUGR rat pups, whereas the arterial sensitivity to the exogenous NO donor DEA/NO was higher in IUGR vs. Control rat pups. Despite relatively low levels of RhoA and Rho-kinase II proteins in the arterial tissue of IUGR rat pups, the decrease in contractile responses, elicited by the Rho-kinase inhibitor Y27632, was equally pronounced in the arteries of rat pups from both IUGR and Control groups. Thus, IUGR, caused by maternal nutritional restriction during pregnancy, causes no pronounced changes in the regulation of systemic vascular tone during the early postnatal period.
Risk factors associated with environmental exposure, especially during critical periods of intrauterine development, affect fetal development and increase the risk of certain diseases in adulthood including cardiovascular diseases (CVD). Hypoxia is considered the most common and clinically significant form of intrauterine stress that causes systemic pathological changes, in 78% of cases associated with cardiovascular system disorders. The purpose of this study was to evaluate the effects of acute hypoxia on the 10th day of gestation on heart rate and its regulation in rats' offspring of prepubescent and pubertal age, as well as to analyze the dependence of resulting disorders on gender. By the beginning of puberty the heart rate of rats survived prenatal hypoxia was significantly higher than in control accompanied by significant decrease in heart rate variability (dX) which naturally leads to stress index (SI) increase indicating growing sympathetic activity in heart rhythm regulation. At the same time the base heart rate in animals suffered intrauterine hypoxia turned out to be lower than in control. The fact that matured animals of both sexes, survived intrauterine hypoxia in early organogenesis, also show changes in dX and SI indicates long-term and irreversible disorders in heart rhythm regulation. Thus hypoxia during early organogenesis is of a programming nature potentially increasing the risk of developing CVD in adult animals. Moreover the autonomic system balance shift towards the activation of sympathetic tone was more pronounced in females making them more vulnerable to the risk of developing cardiac pathology in puberty.
ACTH/MSH-like peptides (melanocortins) have a wide range of neurotropic effects, including effects on learning and memory processes, neuroprotection, emotional state and pain sensitivity. Present work is aimed to compare the effects of peptides, the structure of which includes a natural fragment of ACTH and a stabilizing tripeptide PGP. The peptides ACTH4–7PGP (Semax), ACTH6–9PGP, and ACTH7–10PGP were used in the work. The effects of these peptides on the exploratory behavior, anxiety level and pain sensitivity of white rats, as well as on the protein levels of the neurotrophic factors BDNF (brain derived neurotrophic factor) and VEGF (vascular endothelial growth factor) in primary neuron cultures were studied. A comparative study of the effects of analogs of different ACTH/MSH fragments revealed both similarities and differences in their neurotropic activity. The peptides structure of which includes a sequence of ACTH4–7 or ACTH6–9 have nootropic, anxiolytic and analgesic activity, and also cause an increase in VEGF levels in the culture of hippocampal neurons. The peptide containing the ACTH7–10 sequence in the structure exhibits anxiolytic activity, increases exploratory behavior, does not affect pain sensitivity and has a stimulating effect on BDNF and VEGF levels in neuronal cultures. The data obtained indicate that different parts of the N-terminal region of the ACTH molecule are responsible for the manifestation of certain neurotropic effects of melanocortins. The results of the study can be used in the development of therapeutics based on natural melanocortins.
One of the informative and widely used approaches to understanding the pathogenetic (including neurobiological) mechanisms of schizophrenia is the study of patients with clinically high risk (CHR) for the disease. The power and topography of the theta rhythm event-related synchronization (ERS) related to peripheral stimulus that must be remembered (memory-guided saccades/antisaccades paradigm) have been studied in the groups of 20 mentally healthy subjects and 20 patients with CHR. The analysis was carried out according to the Pfurtscheller method. Based on the saccades latency value and the error numbers, the task performance was decreased in patients with CHR compared to healthy subjects. Intergroup differences by theta rhythm ERS magnitude and topography were found for three consecutive delay period intervals (900 ms each) before saccades to the right and antisaccades to the left. The findings are considered as being the reflection of violations of the spatial attention and working memory maintaining in CHR patients that has a certain interhemispheric asymmetry. It has been suggested an activation of the compensatory processes and the cognitive control reorganization of the fronto-parietal networks with predominantly right hemisphere preservation at the early stage of schizophrenia development.
