bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Molecular and Genetic Mechanisms of Action of the α2-Adrenergic Agonist Mafedine in Experimental Traumatic Brain Injury in Rats
Authors: Sysoev Yu. I. , Shustov M. V. , Prikhodko V. A. , Shitc D. D. , Puchik M. M. , Okovityi S. V.
Published: April 2024

Neurological impairments due to traumatic, vascular, or neurodegenerative brain diseases have a high prevalence worldwide. Among them are motor, cognitive, and mental disorders, which have a serious negative impact on the working and social activities of the patients. This calls for the search and development of novel effective neuroprotective agents. Previous studies have shown the pyrimidine-derived α2-adrenergic agonist mafedine to be highly effective for the amelioration of neurological deficits in experimental traumatic brain injury (TBI) in rats. Despite the results of the previous works favouring the major role of the α2 adrenergic receptor activation in the mechanism of action of mafedine, the search for additional molecular targets is an important part of the development of any drug to be used in clinical practice. In this work, we evaluated the effects of 7 day-long course administration of mafedine (2.5 mg/kg b.w.) on the expression of brain-derived neurotrophic factor (BDNF), the proinflammatory cytokines interleukin (IL)-1β, -6, tumour necrosis factor (TNF)-α, and the α2A, α2B, and α2C α2-adrenergic receptor subtypes in the brain cortex of rats subjected to TBI, using the reverse-transcription real-time polymerase chain reaction method. TBI was modelled by the controlled cortical impact technique in an open area of sensorimotor cortex of the left brain hemisphere. Behavioural alterations in the injured animals were assessed in the Open field test, and the fore- and hindlimb motor function, in the Limb placing, Cylinder, and Beam walking tests. Our experiments show that TBI causes severe motor impairments as well as decreases exploration in rats. Besides, at post-TBI day 7, a reduction in the expression of all analyzed genes is seen, which is the most pronounced in the contralateral (uninjured) hemisphere. Course administration of mafedine (2.5 mg/kg b.w.) resulted in moderate stimulation of the injured rats’ behaviour, increased exploratory activity compared to controls, and improved sensorimotor deficit as assessed by the Beam walking test. Gene expression analysis results indicated that mafedine decreased α2B-adrenergic receptor, TNF-α, and IL-6 expression in the injured hemisphere. At the same time, compared to rats with TBI having received no treatment, mafedine-treated animals exhibited higher α2B-adrenergic receptor and IL-1β expression in the injured rather than the intact hemisphere. These results confirm the previously observed neuroprotective activity of mafedine and imply that it may exert its effects via suppression of α2B-adrenergic receptor and proinflammatory cytokine expression in the injured brain hemisphere, at the same time increasing their expression in the intact one.
Modulating Effect of the Leptin Fragment 116–122 on Testicular Steroidogenesis in Male Rats
Authors: Bakhtyukov A. A. , Lebedev I. A. , Kuznetsova V. S. , Derkach K. V. , Shpakov A. O.
Published: April 2024

Adipokine leptin plays an important role in the regulation of the reproductive system. It stimulates the activity of the hypothalamic-pituitary-gonadal axis by indirectly acting on GnRH-secreting neurons and modulates testicular steroidogenic function by binding to leptin receptors in Leydig cells. A leptin fragment 116–122 (LF) including the main receptor-binding determinants of this adipokine, normalizes metabolic parameters in animals with diet-induced obesity. However, its ability to influence the steroidogenic function of the testes, including through interaction with GnRH neurons of the hypothalamus, has not been studied. The aim of this work was to study the effects of a single and three-day intranasal administration of LF (200 μg/rat) on the blood testosterone level and the expression of steroidogenic genes in the testes in mature male Wistar rats. To evaluate the effect of LF on testicular steroidogenesis upon stimulation with human chorionic gonadotropin (hCG, 15 IU/rat, s/c), a stimulator of testosterone synthesis and an antagonist of the GnRH receptor cetrorelix (75 μg/kg, s.c.) an inhibitor of testicular steroidogenesis. It has been shown that LF increases the level of testosterone in the blood after a single injection, and after a three-day administration it enhances the steroidogenic effect of hCG. LF and hCG increased the expression of the Star gene encoding the key regulatory protein of steroidogenesis StAR. Administration of cetrorelix reduced testosterone levels and Star expression, and compensatory increased expression of the luteinizing hormone receptor gene. The potentiating effect of LF on hCG-induced stimulation of testosterone levels and Star expression was not detected under conditions of GnRH antagonist treatment. Thus, LF is capable of stimulating steroidogenesis in rat testis by itself and potentiating the steroidogenic effects of hCG. Since its effects are suppressed in the presence of a GnRH antagonist, there is reason to assume that the effect of LF is realized through stimulation of hypothalamic GnRH neurons.
The Effect of Spinal Cord Injury on P2 Signaling in the Cholinergic Synapse
Authors: Khairullin A. E. , Efimova D. V. , Eremeev A. A. , Sabirova D. E. , Grishin S. N. , Ziganshin A. U.
Published: April 2024

It is known that in spinal motor neurons, after damage to the upper level of the spinal cord, neuronal degradation occurs, accompanied by axon degeneration. In the present study, the functional integrity of neuromuscular transmission was assessed by the method of stimulation mechanomiography. We demonstrated a decrease in the modulating activity of ATP in the cholinergic synapse due to spinal cord injury (a model of spinal cord contusion injury) in comparison with hypodynamia (a model of anti-orthostatic hanging of the hind limbs). The demonstrated abnormal modulation of the neuromuscular junction by purines provides evidence of axon degeneration and suggests that trans-synaptic degeneration of motor neurons may occur below the level of spinal cord injury in patients with similar injuries.
Motor Synergies in the Control System of Complex Sports Balance Postures
Authors: Moiseev S. A. , Mikhaylova E. A.
Published: April 2024

The paper presents the motor synergies’ structure at the muscular and kinematic levels of their study during performing various sports balance postures. The features of the formation and modification of synergetic modules depending on the motor task are considered. An attempt is made to combine some computational aspects applied according of various concepts of synergetic control. The tools for identifying and analyzing synergy parameters included regression analysis and data factorization methods. It has been established that differing in biomechanical structure balance exercises can be realized using common patterns of kinematic synergies spatial organization, however, at the muscular level, the existence of common spatial activation profiles is not obvious. The presence of several different time patterns of synergy activation in the structure of each balance exercise has been revealed, which may be associated with various motor control strategies in the central nervous system. The structure of kinematic synergies may be influenced by artificial degrees of freedom restriction, unrelated to central control processes. It is shown that the inclusion of the concept of “variables’ area” in the motor control modular organization theory contributes to the convergence of existing motor control concepts based on synergy principle.
Impakt of Ozone on the Oxyge Affinity Blood Properties and Prooxidant–Antioxidant Balance under Effect of H2S-Generating System
Authors: Zinchuk V. V. , Biletskaya E. S.
Published: April 2024

Hydrogen sulfide belongs to the group of signaling agents called gaseous transmitters and plays an important role in many physiological processes, in particular, in the realization of oxygen-dependent mechanisms. The aim of this study was to evaluate the significance of hydrogen sulfide in the effect of ozone on the oxygen affinity blood properties and the prooxidant-antioxidant balance in vitro experiment. Ozone (6 mg/L concentration) and drugs that affect the synthesis of hydrogen sulfide (propargylglycine, sodium hydrosulfide and its combination with nitroglycerin) were used. The use of propargylglycine, an inhibitor of the synthesis of hydrogen sulfide, leads to a decrease in the effect of ozone on the blood oxygen transport function (decrease in PO2, SO2, P50real). When sodium hydrosulfide is added, the effect of this gas on these parameters does not increase, but in its combination with nitroglycerin, the effect of ozone on the blood oxygen transport function increases. Propargylglycine does not affect the prooxidant-antioxidant balance under the conditions of the experiment, and donors of hydrogen sulfide and nitrogen monoxide increase the activity of catalase. Propargylglycine under the action of ozone leads to a decrease in the level of nitrate/nitrite, and sodium hydrosulfide increases their concentration. The combination of sodium hydrosulfide and nitroglycerin leads to the accumulation of hydrogen sulfide in the blood plasma.
GCaMP – a Family of Single-Fluorophore Genetically Encoded Calcium Indicators
Authors: Erofeev A. I. , Vinokurov E. K. , Vlasova O. L. , Bezprozvanny I. B.
Published: April 2024

Single fluorophore genetically encoded calcium indicators (GECIs) such as GCaMP are widely utilized tools for investigating neuronal activity. Their primary advantage lies in their capacity to provide real-time and highly sensitive responses to fluctuations in intracellular calcium ion concentrations. This characteristic is of significant importance when studying neuronal processes and ensembles, wherein calcium signals play a crucial role in information transmission. This comprehensive review focuses on the GCaMP family, encompassing an analysis of their various types, distinctive features, and potential applications for visualizing neuronal activity. Special attention is dedicated to the ongoing advancements in GCaMP technology, particularly the endeavors to expand their spectral properties and enhance their capability to detect high-frequency spike activity.
Reaction of Kidney Medullary Laminin to Prolonged Dehydration of Rats
Authors: Khegay I. I.
Published: April 2024

Laminin is the main water-soluble protein in the basement membrane of epithelial tissue. The content of laminin in the renal parenchyma was studied in rats that were on an alternative water diet for 60 h with excessive water intake or a complete lack of drinking water in the food. It has been shown that the osmotic concentration of urine, which develops as a result of water deprivation, is accompanied by a quantitative change in the composition of laminin. It has been established that the amount of laminin beta chain increases in the kidney medulla of dehydrated rats. This effect is observed only in WAG rats with normally expressed vasopressin gene and is absent in mutant Brattleboro rats unable to synthesize the hormone. The increase in the level of beta-laminin also does not extend to the cortical substance. Based on the original and new data, it is assumed that laminin, as a key regulatory element in the basement membrane of the tubular epithelium, participates in the adaptive reaction of the concentrating system of the kidney to conditions of prolonged dehydration. Hyperhydration does not affect the level of laminin in the renal parenchyma.
Decrease in Muscle Mass in Diet-Induced Visceral Obesity in Male Wistar Rats: Relationship with Hormonal and Metabolic Parameters
Authors: Mityukova T. A. , Basalai A. A. , Chudilovskaya K. N. , Poluliakh O. Y. , Shcherbakov Ya. V. , Kastsiuchenko M. S.
Published: April 2024

Decrease in muscle mass, as a rule, develops with the aging of the body, but in obesity the signs of decrease in mass and functional activity of the skeletal muscles are also registered, which requires experimental research. The aim of the work was to study the effect of diet-induced obesity and health variants of its correction on mass-metric and metabolic tissue parameters of musculus triceps surae in male Wistar rats. The experiments were carried out on sexually mature male Wistar rats and included the study of mass-metric, metabolic and hormonal indices characterizing the state of muscle tissue under the standard (Std, 16 weeks) and high-caloric diet (HCD, 16 weeks), during the transition from HCD to standard diet (HCD/StD, 8/8 weeks), when physical activity in the form of running on a treadmill was added (StD + running, HCD + running and HCD/StD + running, 8/8). Prolonged high-caloric diet led to the development of visceral obesity and decreased musculus triceps surae mass in male Wistar rats. Metabolic shifts were registered in the skeletal muscles during HCD, such as an increase in glucose, lactate, lactate dehydrogenase activity, and lipid peroxidation. Visceral obesity was accompanied by a decrease in serum testosterone content, but the concentration of the hormone in muscle tissue remained relatively stable. Application of moderate physical activity in HCD did not lead to correction of visceral fat mass, did not prevent decrease in muscle mass, but caused normalization of biochemical indices in muscle tissue and serum testosterone level. The most adequate correction of visceral obesity, muscle mass and biochemical indices in muscle tissue in male rats was achieved by switching from a high-caloric to a balanced diet regardless of physical activity. Thus, correction of diet-induced visceral obesity, muscle mass and associated metabolic shifts in male Wistar rats requires a transition to a balanced diet.
Genome Instability of Hippocampal and Bone Marrow Cells in Male Mice after the Action of Immobilization and Pheromonal Stressor
Authors: Shcherbinina V. D. , Bakulevskiy B. V. , Glinin T. S. , Daev E. V.
Published: April 2024

Different stressors, affecting the cells of target organs, can lead to genomic instability and even disintegration, which can play a role in the formation of post-stress pathologies. We studied the effect of psycho-emotional stressors (immobilization and mouse stress pheromone – 2,5-dimethylpyrazine) on the DNA integrity of hippocampal and bone marrow cell in male mice of CD1, CBA and C3H strains. Cytogenetic and immunocytochemical methods (alkaline comet assay, ana-telophase analysis of mitotic disturbances and analysis of γH2AX foci) were used. It is shown that the classic mouse stressor (immobilization or restraint), similar as 2,5-dimethylpyrazine, damages the genome of the cells of both organs studied. The destabilization of the cell genome of various organs is considered as an essential stage in the development of a stress response, which is an attempt of the organism to adapt to extreme environmental influences.
Comparative Analysis of Disorders of Heart Rhythm Regulation Mechanisms Induced in Newborn Rats by Nickel Chloride and the Acetylcholinesterase Inhibitor Physostigmine (Eserine)
Authors: Kuznetsov S. V. , Kuznetsova N. N.
Published: April 2024

A comparative analysis of heart rate variability (HRV) indices after injection of the acetylcholinesterase inhibitor (AChE) physostigmine (¾ LD50) and the T-type calcium channel blocker (T-VDCC) Ni2+ (ED100) into animals was performed in experiments on 3-day-old newborn rats. Both drugs cause phenomenologically similar pathological heart rhythm with significant bradycardia complexes (PHRBC). Analysis of HRV indices showed that the disturbance of heart rhythm regulation mechanisms in NiCl2 poisoning of rats and in cholinoreactive structure activation caused by AChE inhibition develop according to a similar pattern. In both cases there is a decrease in the total power of the spectrum and the absolute power values of the LF (predominantly sympathetic) and HF (parasympathetic influences) bands. Significant decrease in the level of nerve influences leads to the fact that the dominant role in the regulation of heart rhythm begins to play neurohumoral factors (VLF-band). It was found that under conditions of premedication with H- or M-cholinolytics, when rats do not develop cardiac rhythm disturbances, the initial decrease in the severity of neurohumoral and subsequent increase in sympathetic and, to a lesser extent, parasympathetic influences is common. In this case, vagosympathetic balance is not decisive. In case the influence of neurohumoral factors increases after premedication, then later there is a decrease in the proportion of nerve influences and the occurrence of PHRBC. The obtained data suggest that in newborn rats both direct blockade of T-VDCC and changes in ICaT current mediated through M3-subtype muscarinic cholinoreceptors lead to disruption of pacing and development of PHRBC.
Mechanosensory Structures in the Mechanotransduction System of Muscle Fibers
Authors: Mirzoev T. M. , Shenkman B. S.
Published: April 2024

The ability of skeletal muscles to sense mechanical stimuli and respond to them by changing intracellular electrochemical and biochemical processes (mechanotransduction) is of crucial importance for the regulation of physiological processes in muscle fibers. This review describes the main sarcolemmal, sarcomeric, and cytoskeletal mechanosensitive structures and analyzes mechano-dependent signaling pathways and mechanisms involved in the regulation of gene expression as well as muscle protein synthesis and degradation. The final part of the review formulates specific questions in the field of muscle mechanotransduction that need to be addressed in future studies. Understanding of skeletal muscle mechanotransduction is necessary for the development of effective measures aimed at the treatment of muscular dystrophies, sarcopenia, and prevention of disuse-induced muscle atrophy.
Effect of Neurohypophyseal Hormones on Excretion of Proteins by the Kidneys
Authors: Karavashkina T. A. , Balbotkina E. V. , Kovaleva T. V. , Kutina A. V.
Published: April 2024

Vasopressin (VP) is one of the main factors affecting intraglomerular hemodynamics, filtration pressure and the state of mesangial cells and contributing to the progression of proteinuria. The aim of this work was to study the effect of neurohypophyseal hormones (VP and oxytocin) on urinary protein excretion. Experiments were performed on Wistar rats, healthy and with microalbuminuria caused by minimal damage to the glomerular filter. Microalbuminuria was modeled by administration of D-nitroarginine methyl ester (D-NAME, 50 mg/kg, intraperitoneally). VP (0.05 and 1.5 nmol/kg) and oxytocin (0.15 nmol/kg) were administered to rats intramuscularly, V2-antagonist (15 nmol/kg) and V1a-antagonist (20 nmol/kg) intraperitoneally. To reduce the level of endogenous VP, animals were given water to drink (10 ml/kg), urine was collected for 2 h, and the levels of total protein, albumin, β2-microglobulin, and immunoglobulin G (IgG) were analyzed. In healthy rats, VP at a dose of 0.05 nmol/kg and oxytocin did not affect albumin excretion, but VP at a dose of 1.5 nmol/kg provoked microalbuminuria. In a model of impaired properties of the glomerular filter caused by the D-NAME administration, VP at a dose of 0.05 nmol/kg and oxytocin led to the normalization of albumin excretion, and VP at a dose of 1.5 nmol/kg caused pronounced proteinuria, albumin excretion increased by 100 times, IgG – by 10 times. Blockade of V2 receptors aggravated protein loss caused by D-NAME and VP (1.5 nmol/kg), while blockade of V1a receptors prevented it. Thus, at high concentrations in the blood, VP enhances protein filtration in the kidney. This effect is mediated by V1a receptors and, depending on the barrier properties of the glomerular filter, leads to the development of microalbuminuria or severe proteinuria. Oxytocin and VP at a dose at which it predominantly activates V2 receptors have an antiproteinuric effect. The revealed effects of neurohypophyseal hormones on albumin excretion open up new promising therapeutic targets for the correction of glomerular dysfunctions.
Analysis of Behavior and Brain Neuronal Density in B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J Mice Modeling Parkinson’s Disease
Authors: Rozhkova I. N. , Okotrub S. V. , Brusentsev E. Yu. , Rakhmanova T. A. , Lebedeva D. A. , Kozeneva V. S. , Khotskin N. V. , Amstislavsky S. Ya.
Published: April 2024

Parkinson’s disease (PD) is a progressive age-related neurodegenerative pathology of the central nervous system, characterized by a selective loss of dopaminergic neurons of the nigrostriatal pathway and by the presence of specific inclusions (Lewy bodies) in dopamine neurons. To study the mechanisms of this pathology and to search for possible ways to correct it, genetic models of PD in mice have been created. Transgenic mice of the B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J strain (referred as B6.Cg-Tg further in the text) represent a model of PD, have the A53T mutation in the human alpha-synuclein gene. The aim of this work was to study the locomotor activity and the level of anxiety, as well as the density of neurons in the brain of male B6.Cg-Tg mice at the age of six months. Wild type C57BL/6J mice of the same sex and age were used as controls. The results of the current study demonstrate that B6.Cg-Tg mice are characterized by the high locomotor activity and the low anxiety. Besides, a selective decrease in the density of neurons in the subventricular zone, the substantia nigra, as well as the CA1, CA3, CA4 zones and the granular layer of the dentate gyrus of the hippocampus was observed in these mice. Thus, mice of the B6.Cg-Tg strain at the age of six months only partially correspond to the main pathophysiological signs of PD. Decrease in the density of neurons in the substantia nigra, as well as in the CA1 and CA3 zones of the hippocampus of B6.Cg-Tg mice resemble similar changes in PD. However, these mice demonstrated neither bradykinesia nor high level of anxiety.
Influence of NO Synthase Inhibitors on Serotonin Release in the Medial Prefrontal Cortex during the Formation and Generalization of the Conditioned Fear Response in Rats
Authors: Saulskaya N. B. , Susorova M. A. , Trofimova N. A.
Published: April 2024

Serotonergic and nitrergic systems of the medial prefrontal cortex (mPFC) are involved in the control of fear generalization, but their local interaction during this function has been little studied. The aim of the work was to study the effect of blockade of endogenous nitrergic signals on serotonin release in the mPFC during the acquisition of a conditioned fear response (CFR – a fear model) and on the dynamics of its generalization. In male Sprague-Dawley rats using intracranial microdialysis in vivo and high-performance liquid chromatography with electrochemical detection, we found that the intra-mPFC infusion through the dialysis probe of the NO synthase inhibitor N-ω-nitro-L-arginine (NA, 0.5 mM) and selective neuronal NO synthase inhibitor N-ω-propyl-L-arginine (NPLA, 2mM) decreased the basal level of extracellular serotonin in the mPFC and reduced its rise, caused by the CFR acquisition (a paired presentation of a conditioned cue (CS+) and inescapable footshock). The intra-mPFC infusion of NA and NPLA increased animals’ freezing to a differential cue (CS–) not associated with footshock, during the first test, carried out 70 minutes after the CFR acquisition, but reduced it during repeated testing a day after the infusion, without changing freezing of the same animals to the potentially dangerous CS+. The data obtained indicate the involvement of endogenous NO in the activation of serotonin release in the mPFC, caused by the CFR acquisition. In addition, they show that the blockade of endogenous nitrergic signals of the mPFC, which enhances the initial generalization of the fear reaction, contributes to the extinction of the generalized fear, possibly due to inhibition of the serotonin release in the mPFC.
Mechanisms of Antiproliferative Action of Streptococcal Arginine Deiminase Against Jurkat Lymphoblastic Leukemia Cells
Authors: Starikova E. A. , Mammedova J. T. , Ozhiganova A. , Burova L. A. , Kudryavtsev I. V.
Published: April 2024

Arginine deprivation strategy is considered as a promising trend in cancer therapy. The aim of the study was to investigate the influence of streptococcal arginine deiminase on Jurkat lymphoblastic leukemia cells. The effects of the supernatants of the destroyed streptococci of the original strain expressing arginine deiminase and its isogenic mutant with the inactivated arcA gene were compared. Cell proliferation was evaluated in an MTT-test. The remaining parameters were examined using flow cytometry. The cell cy-cle changes were studied using DAPI dye and anti-cyclin A2 antibodies. The autophagy intensity was assessed using the LysoTracker ™ Green DND-26 reagent. To investigate cell viability DAPI staining was performed. Streptococcal arginine deiminase suppressed proliferative activity Jurkat lymphoblastic leukemia cells, increased the proportion of cells in the G0/G1 phases, reduced S/G2 phases proportion of cells and enhanced autophagy, without declaing viability. Arginine supplementation leveled the effects of the enzyme. The obtained results open up the possibility of using arginine-hydrolyzing activity of the streptococcal enzyme for combined therapy of oncological diseases.
Steroidogenic Effect of Luteinizing Hormone Receptor Agonists and Metformin in Male Rats with Androgenic Deficiency Caused by Diet-Induced Obesity
Authors: Bakhtyukov A. A. , Derkach K. V. , Lebedev I. A. , Sorokoumov V. N. , Shpakov A. O.
Published: April 2024

In obese men, along with metabolic disorders and insulin resistance, testosterone levels are decreased and reproductive system functions are impaired. One of the ways to correct them may be the use of agonists of luteinizing hormone receptor (LHR) and antidiabetic drugs, but the mechanisms of their effect on the hypothalamic-pituitary-gonadal axis have not been studied enough. The aim of the work was to study the effects of long-term MF therapy (5 weeks, 120 mg/kg) and five-day treatment with LHR agonists, such as human chorionic gonadotropin (hCG, 20 IU/rat/day, s.c.) and allosteric agonist TP03 (15 mg/kg/day, i.p.), on the blood testosterone levels and the expression of testicular and pituitary genes in male rats with long-term diet-induced obesity (DIO). TP03 moderately stimulated testosterone production in male rats with DIO without having an inhibitory effect on LHR expression in the testes and only weakly reducing the expression of the LH β-subunit gene in the pituitary gland. After a single administration into DIO-rats, the steroidogenic effect of TP03 was comparable to that in the control group, but after a five-day administration, it was significantly inferior to it. In DIO-rats, the steroidogenic effect of hCG after a single administration was lower than that in the control, but comparable to that after a five-day administration of hCG, and significantly exceeded the corresponding effects of TP03. Unlike TP03, hCG significantly reduced LHR expression in the testes and more pronouncedly inhibited LH expression in the pituitary gland. MF treatment restored the androgenic status without significantly affecting the expression of steroidogenesis genes in the testes. There was no increase in the steroidogenic effects of both LHR agonists in the MF-treated groups. The results obtained indicate the prospects for the use of TP03 and hCG to stimulate testicular steroidogenesis and the effectiveness of MF therapy to normalize testosterone production in DIO, which can be used to correct reproductive disorders in obesity. At the same time, in DIO, the combined use of MF and LHR agonists seems to be inappropriate.
Comparison of the Effect of Keeping Rats in the Mountains and on the Plain on the Development of Streptozotocin-Induced Diabetes and Gastric Ulceration
Authors: Podvigina T. T. , Komkova O. P. , Vetrovoy O. V. , Yaruskina N. I. , Filaretova L. P.
Published: April 2024

Hypoxia can correct the development of diabetes and its complications in animals and humans, and diabetes exacerbates the gastric ulceration. However, the effect of hypoxia on the gastric ulceration in diabetes remains unknown. The task of the work was to compare the effect of keeping rats in the mountains under moderate natural hypoxia and on the plains on the development of type 1 diabetes and the gastric ulceration. Two weeks after the rats acclimatized to hypoxia (Elbrus region, 2125 m above sea level), they were injected with streptozotocin (STR, 50 or 70 mg/kg) or its vehicle. Simultaneously, rats on the plains were injected with STR (or its vehicle) at the same doses. Indomethacin (IM, 35 mg/kg) was administered two weeks after STR or its vehicle injection in rats after 24 h of fasting, both in the mountains and on the plains, which led to the gastric erosion formation 4 h later. The injection of STR (50 and 70 mg/kg) caused a dose-dependent increase in blood glucose levels in rats both in the mountains and on the plains, which indicates the development of diabetes of varying severity. In rats on the plains the administration of STR (50 and 70 mg/kg) led to a dose-dependent increase in the area of erosions induced by IM compared with those in control animals (STR vehicle). In rats in the mountains, an aggravation of gastric mucosal injury caused by IM was observed, both in control rats (STR vehicle) and in animals with STR-induced diabetes, compared with the gastric injury in rats of the corresponding groups on the plains. The greatest increase in the proulcerogenic effect of STR in the mountains was observed when it was administered at a dose of 70 mg/kg. Thus, persistent moderate hypoxia may lead to an increase in IM-induced gastric ulceration in rats with type 1 diabetes, and, in addition, by itself exacerbate the ulcerogenic effect of IM.
Behavioral, Genomic and Neurochemical Deficits Evoked by Neurotrauma in Adult Zebrafish (Danio rerio)
Authors: Ilyin N. P. , Galstyan D. S. , Demin K. A. , Kalueff A. V.
Published: April 2024

Traumatic brain injury (TBI) is a serious biomedical problem with high prevalence and mortality risks. Understanding TBI in traditional (e.g., rodent) animal models often presents challenges due to the complexity of their brain and its limited regenerative capabilities. Here, we present novel data obtained using the zebrafish TBI model based on a stab wound of telencephalon, aiming to investigate behavioral and molecular consequences of TBI in zebrafish. Four days following the injury, adult zebrafish displayed hypolocomotion in the novel seen tank test and impaired working memory in the Y-maze test, paralleling behavioral deficits in rodent models and human TBI patients. Molecular analyses of key genes involved in the inflammatory response and cell death pathways revealed a remarkable upregulation of the interferon-stimulated gene 15 (isg15) in the injured telencephalon, a general biomarker for neuronal damage. Furthermore, noradrenaline (but not dopamine or serotonin) levels in whole-brain tissue declined following TBI, likely contributing to the observed cognitive deficits and implicating neurotransmitter dysregulation in TBI pathogenesis.
Molecular Genetic Mechanisms of Circadian Rhythm Regulation and Their Role in Psychopathology
Authors: Smirnova K. V. , Chizhova N. D. , Gerasimova E. V. , Kalueff A. V. , Amstislavskaya T. G.
Published: April 2024

Circadian rhythms are cyclic fluctuations in the intensity of biological processes associated with the change of day and night, to which many organisms have adapted during the evolution. Disturbances in circadian rhythms are triggered by both environmental factors (e.g., altering the time zone or the length of day/night) and disrupted internal regulation of cycles (e.g., mutations of key clock genes). These changes can lead to the pathogenesis of various diseases, including psychopathologies. Since the mechanisms underlying circadian regulation are rather evolutionarily conservative, experimental animal models are actively used to probe these processes and their relationship with psychopathologies. Here, we discuss the regulation of circadian rhythms, as well as their cross-taxon similarities and differences between mammals and teleost fish (zebrafish, Danio rerio). We also discuss recent findings on molecular genetic mechanisms underlying the regulation of circadian rhythms and their link to pathogenesis of mental disorders in humans and model organisms.
Mice Lacking TAAR1 Show No Early Behavioral Response to Acute Restraint Stress
Authors: Aleksandrov A. A. , Vinogradova E. P. , Simon Yu. A. , Aleksandrov A. Yu. , Knyazeva V. M. , Stankevich L. N. , Kozyreva A. V.
Published: April 2024

The role of the TAAR1 receptor, one of the trace amine-associated receptors (TAARs) family, in the formation of the behavioral component of the stress response was studied. The behavior of female TAAR1 knockout mice and wild-type (WT) mice was investigated in tests of elevated plus maze and elevated zero maze (EPM and EZM) and forced swimming test (FST) under normal conditions and after uncontrolled restraint stress exposure for 30 min. In the EPM test, the initial level of locomotor and exploratory activity, as well as the anxiety, was identical in both groups of mice. In the EZM test, the initial indicators of anxiety in female TAAR1 KO mice compared to female WT mice were higher, and locomotor activity was lower. When testing mice in the EZM 30 minutes after the end of stress exposure, it was found that the anxiety in female WT mice sharply increased, and the indicators of locomotor activity and exploratory behavior significantly decreased. The behavioral indicators in the EZM test in TAAR1 KO mice before and after stress were identical. A pronounced behavioral component of the stress response was observed in both TAAR1 KO and WT mice during testing in EPM. There were no significant differences between TAAR1 KO and WT mice during testing in EPM four hours after stress exposure. In the FST test the latency to the first immobility was initially longer in TAAR1 KO mice compared to the WT mice, but 24 h after the stress this indicator has significantly decreased. As a result, TAAR1 KO and WT mice no longer differed in all behavioral indicators in the FST. Three weeks after acute restraint stress, both TAAR1 KO and WT groups showed a significant increase in immobility duration and a decrease in latency to the first immobility, however no difference between the both groups of animals were found. Thereby, we found the complete absence of behavioral change immediately after stressor exposure in TAAR1 KO compared to the WT mice.
Experimental Models of Mitochondrial Dysfunction Disorders in the Pathogenesis of CNS Diseases on Zebrafish
Authors: Yushko L. V. , Kotova M. M. , Vyunova T. V. , Kalueff A. V.
Published: April 2024

Mitochondrial dysfunctions are associated with the pathogenesis of various brain disorders, including Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, Leigh syndrome and autism spectrum disorder. For the study of mitochondrial dysfunction and the development and testing of new therapeutic strategies, in vivo studies with zebrafish (Danio rerio) are of particular interest, due to their biological characteristics, practicality in laboratory maintenance, and high throughput. Here, we discuss genetic and pharmacological models of common mitochondrial dysfunctions and related neurological disorders in rodents and zebrafish, focusing of the growing utility of these fish in modeling mitochondrial pathogenesis of various CNS diseases.
Peculiarities of Fear Memory Disturbance in Male and Female Disc1-Q31L Mice
Authors: Chizhova N. D. , Smirnova K. V. , Dubrovina N. I. , Kalueff A. V. , Amstislavskaya T. G.
Published: April 2024

Depressive disorder is the most common psychopathology that can coexist with other mental illnesses such as post-traumatic stress disorder. It has been shown that there are gender differences in susceptibility to these psychopathologies. Mice of the mutant strain Disc1-Q31L are characterized by depressive-like behavior and disruption of the molecular pathways involved in the processes associated with fear memory. Gender and interstrain differences in the processes of learning and extinction of the conditioned response of passive avoidance were studied in male and female Disc1-Q31L mice and control C57BL/6 mice. It was shown that male and female mice of both strains learned equally well the conditioned response of passive avoidance, but differed in fear memory extinction, the ability to form a new safety memory trace in the previously dangerous dark compartment of the setup. However, there was a deficit in the extinction of the conditioned response of passive avoidance in C57BL/6 females compared to males, as well as interstrain differences in the dynamics of extinction in both females and males. Disc1-Q31L males reached full extinction later than C57BL/6 males, while Disc1-Q31L females did not exhibit extinction during the 24 days of the test. Thus, this work shows the interaction of the effect of gender and the Disc1-Q31L mutation on the processes of fear memory extinction.
Baclofen and 4-Phenylpyrrolidone Derivative GIZH-290 Attenuates Compulsive-Like Behavior in Mice
Authors: Kudryashov N. V. , Volkova A. V. , Kozin Ya. S. , Shimshirt А. А. , Naplekova P. L. , Korolev А. О. , Voronina T. А.
Published: April 2024

Obsessive-compulsive disorder (OCD) is a mental disease characterized by the obsessions which cause marked distress or anxiety and/or compulsions intended to alleviate this distress. The results of experimental and clinical studies suggest a possible role of GABAB receptors in the pathogenesis of OCD, making it relevant to study the effect of ligands of these receptors on the behavior of rodents. Objectives: Studying the effects of GIZH-290 and baclofen in animal models of OCD. Methods. The effects of GIZH-290 (0.01, 0.1, 1 mg/kg, i.p.) and baclofen (0.1, 1, and 5 mg/kg, i.p.) were studied in the marble burying test and the rotarod test, as well as in the 8-OH-DPAT-induced decrease in spontaneous alternation in mice. Results. Baclofen and GIZH-290 attenuated compulsive-like behavior in mice by reducing the number of buried marbles in the marble burying test at all tested doses. However, the effect of baclofen at a dose of 5 mg/kg was accompanied by a disruption of the animals’ motor coordination in the rotarod test. At the same time, neither baclofen nor GIZH-290 attenuated 8-OH-DPAT-induced (2 mg/kg, i.p.) decrease in spontaneous alternation behavior in mice. On the contrary, baclofen at a dose of 1 mg/kg exacerbated this disruption. Conclusion. Baclofen and GIZH-290 have anticompulsive activity in the marble burying test, but not in the 8-OH-DPAT-induced decrease in spontaneous alternation behavior in mice.
The Role of Potassium Channels in the Regulation of the Transport Function of Rats Lymph Nodes during Inflammation
Authors: Lobov G. I.
Published: April 2024

Lymph formed in tissues necessarily passes through lymph nodes (LN), which not only perform an immune function, but also take part in lymph flow through rhythmic high-amplitude contractions. During inflammation, inducible NO synthase (iNOS) is expressed in the lymph nodes, which promotes relaxation of the LN capsule. This study examined the role of KATP- and BKCa-channels in sepsis-induced LN remodeling. Sepsis was induced in rats by cecal ligation-puncture surgery. After 12 and 24 h, mesenteric LN were removed and examined in a myograph. KATP-channels were activated by pinacidil and blocked by glibenclamide. BKCa-channels blocked TEA and activated NS 1619. The strength of tonic contraction of the LN under the action of activators and blockers was assessed. LN of septic rats named low level of tone during standard stretching. Pinacidil led to greater relaxation of LN in septic rats compared to the control group; the effect of glibenclamide was accompanied by an increase in tone. Pinacidil combined with glibenclamide did not lead to significant changes in LN tone. The use of NS 1619 was accompanied by relaxation of the LN; in the LN of septic rats, the effect was more pronounced. TEA (3 mM) led to an increase in LN tone; the LN of septic rats responded to the use of TEA with a greater contraction. We concluded that NO produced by expressed iNOS in animals with sepsis directly or indirectly activates KATP- and BKCa-channels of smooth muscle cells of the capsule in the LN, which leading to hyperpolarization of the smooth muscle cell membrane and their relaxation, which that promotes relaxation of the LN capsule and their hypertrophy of LN. In the future, KATP- and BKCa-channels of smooth muscle cells of the lymph node LN capsule may be a potential target for therapeutic intervention to correct the immune response by slowing down or accelerating the flow of lymph through the LN.
Event-Related Potentials in Cued Go/NoGo Task are Possible Neuromarkers of Monotony
Authors: Pronina M. V. , Starchenko M. G. , Boytsova Yu. A. , Bogdan A. A. , Khomenko Yu. G. , Kataeva G. V. , Shichkina Yu. A. , Kropotov Yu. D.
Published: April 2024

Monotony or mental fatigue occurs during performing low-content and monotonous work, including the work of the operator. It is accompanied by a decrease in the concentration of attention and the speed of its switching, as well as slowing in the processes of perception and motor reactions, which can lead to a loss of vigilance, self-control and the occurrence of drowsiness and, consequently, an increase in the risk of industrial injuries and accidents. In this regard, an urgent task is to develop methods for monitoring the human condition in the process of performing monotonous activities. We investigated the effect of monotony on event-related potentials (ERPs) in the visual cued Go/NoGo test. We analyzed 31-channel EEG data of 25 healthy subjects recorded before and after performing four tests with a total duration of around 1.5 hours, representing the same type of tasks with different instructions and simulating the conditions of monotonous work. After performing four tests, we observe an increase of P2 wave, decrease of the P3 Cue wave and the contingent negative variation (CNV) wave in the Cue condition, as well as the decrease of P300 wave in the NoGo condition. The results obtained in this work are assumed to reflect attenuation in proactive and reactive cognitive control during monotony and allow us to consider the P2, P3 Cue, CNV and P3 NoGo waves as possible candidates for the role of neuromarkers of monotony, which makes it promising to use these indicators in systems for monitoring the human condition during operating work.
Effets of Antihistamines in Adult Zebrafish in Novel Tank Test
Authors: Zhdanov А. V. , Komelkova M. V. , Gorbunova М. А. , Khatsko S. L. , Sarapultsev А. P. , Kalueff А. V.
Published: April 2024

Histamine receptors play pivotal roles in various physiological functions, ranging from allergic responses to memory and sleep regulation, making them important drug targets. While second-generation antihistamines have been successfully used in rodents and humans, investigating their effects in non-traditional animal models enhances our understanding and aids the development of novel drug candidates. In this study, we examined the impact of the first-generation drug chloropyramine and the second-generation drugs loratadine and cetirizine, at concentrations of 1, 5, and 10 mg/L, on adult zebrafish b-ehavior using the novel tank test. All three drugs significantly altered fish locomotor a-ctivity, decreasing distance traveled and average velocity while increasing low acceleration frequency. Chloropyramine at 5 and 10 mg/L and loratadine at 1, 5, and 10 mg/L significantly reduced top entries compared to the control. Additionally, 5 mg/L chloropyramine increased the total duration of top entries, whereas loratadine at 10 mg/L r-educed this behavior compared to controls. Overall, chloropyramine and loratadine e-xhibited a sedative effect typical of antihistamines, while cetirizine solely reduced locomotor activity without affecting other patterns of fish behavior. Thus, cetirizine demonstrated the least impact on the central nervous system among the studied drugs, making it the optimal and safest choice among antihistamines.
Air Cleaning from Organic Compounds Using a Nanofiltration Composite Membrane Based on Cellulose Acetate and a Commercial Membrane of OPMN-P Brand
Authors: Fazullin D. D. , Mavrin G. V. , Shaikhiev I. G.
Published: April 2024

Nanofiltration membranes were used to separate the vapor–air mixture containing organic compounds. The membrane was obtained on a filter paper substrate by pouring with a three-component polymer solution. The surface layers were deposited on the substrate by sequentially alternating the stages of membrane drying. The resulting membrane has hydrophilic properties, the porosity of the resulting membrane is 51%. The membrane thickness determined by SEM was 98 µm. The retention capacity of the membranes was studied by separating model mixtures of ethanol–air and gasoline–air. The membrane permeability of the MAC3 composite membrane during separation of the ethanol–air vapor-air mixture was 11.0 m3/m2h at a pressure of 0.5 MPa. The high retention capacity of the MAC3 composite membrane was established for xylenes, toluene, and heptane; for other compounds, the efficiency is no more than 90%. The average retention capacity of the resulting membrane was 87%. Comparative tests to establish gas separation parameters under similar conditions were carried out with a commercial membrane brand OPMN-P.
Optimization of the Hydrodynamic Regime in the Flow Electrodializator Cell
Authors: Filimonova A. A. , Chichirov A. A. , Pechenkin A. V. , Chichirova N. D.
Published: April 2024

Electrodialysis is a water treatment and wastewater treatment technology that uses an electric field gradient and ion exchange membranes to separate ions in aqueous solutions. Studies conducted using this technology have shown the influence of the hydrodynamic regime on the efficiency of the process, the rate of mass transfer and polarization concentration. The article presents experimental results, mathematical calculations and numerical modeling in the universal software system of analysis by the Ansys finite element method. Theoretical calculated results show a good correlation with the results of hydrodynamic processes in the apparatus obtained experimentally. The hydrodynamic regime in the channel of the electrodialyzer cell has been studied, the influence of the mesh geometry on the distribution of fluid flow over the membrane surface has been shown, and the change in flow velocity and pressure depending on the structure of the mesh has been described.
Polymer Membranes for Vapor-Phase Concentration of Volatile Organic Products of Biomass Processing
Authors: Shalygin M. G. , Kozlova A. A. , Heider J. , Sapegin D. A. , Netrusov A. I. , Teplyakov V. V.
Published: April 2024

The biomass processing is one of the demanded promising technologie including energy carriers and valuable chemical reagents. The developed processes of lignin bio-processing suggest the use of a synthetic biological system that allows obtaining lower aliphatic alcohols through the stage of formation of carboxylic acids. Due to the production of alcohols in the form of dilute aqueous solutions, their recovery and concentration are extremely energy-consuming stages. In this paper, a vapor-phase membrane separation method is considered in application to aqueous solutions containing alcohols and organic acids. The transfer of vapors of water, C1–C4 alcohols and acetic acid through commercial pervaporation and gas separation membranes, which have not been previously studied for this purpose, has been investigated. RomakonTM-102 PM membrane demonstrated the highest separation of water-alcohol mixtures. Based on the experimental data obtained, mathematical modeling of the process of ethanol recovery from triple mixture “water/ethanol/acetic acid” by the vapor-phase membrane method was carried out.