


Volume 110, Nº 7 (2024)
REVIEW
Molecular-genetic markers of neuroglia in traumatic brain injury and their use for assessing functional status of sportsmen
Resumo
Neuroglia performs multiple important functions including maintaining brain homeostasis, metabolism, neuroprotection and modulating neurotransmission. Studying the role of neuroglia is necessary to understand the development of pathological neurodegenerative processes, as well as the restoration of nervous tissue during inflammation or injury. However, the analysis of neuroglial processes is complicated by its high heterogeneity and the lack of a system of biomarkers that make it possible to unambiguously assess the functional state of the nervous system. Here, we analyze data on clinically significant molecular genetic markers of different types of neuroglia, and the prospects for their use in sport physiology, including the assessment of athletes following traumatic brain injuries of varying severity and other types of sport-related traumas.



Gonadotropin-releasing hormone and organs of the immune system
Resumo
As a result of a literature search, the physiological aspects of the gonadotropin-releasing hormone (GnRH) influence on immune organs, such as red bone marrow, thymus, spleen and lymph nodes, were considered. The use of GnRH drugs leads to the replacement of red bone marrow with yellow one with an increase in the content of lymphoid and myeloid progenitor cells. In parallel, processes of osteoporosis occur due to increased bone resorption with corresponding changes in calcium metabolism and a decrease in the density of various bone tissues. At the same time, there are papers reporting no effect of GnRH on bone density and changes in calcium metabolism. GnRH acts on the thymus during embryonic development, and in postnatal ontogenesis, and during inflammation and age-related involution processes. Not only GnRH causes changes in the thymus; the thymus may also influence on the GnRH system. A direct effect of GnRH on spleen cells had not been detected, but the weight of the organ changed as a result of active immunization against GnRH in experiment. Unfortunately, very few articles demonstrate the physiological mechanisms of immunomodulation in such conditions. In any case, the obvious insufficiency and contradictory of publications on each aspect of GnRH effects indicates that they have been poorly studied, and it’s advisabile of further continuing not only applied research, but also fundamental investigations, due to its possible high prospects for creating immune control systems.



Augmented cortisol and antiglucocorticoid therapy in mood disorders: the hippocampus as a potential drug target
Resumo
The pathophysiology of many mood disorders is closely related to abnormal stress response associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol overproduction. The hippocampus, a key structure of the limbic system responsible for both cognitive and emotional spheres, is selectively vulnerable to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration. The antiGC therapy of psychiatric diseases, in particular depressive disorders, may be a useful additional treatment. Among other approaches, targeting glucocorticoid receptors, abounded in the hippocampus, is regarded as highly promising. However, though the preclinical data provide fairly firm evidence to the concept of antiGC therapy for stress-related diseases, clinical studies still are at the proof-of-concept stage. Noteworthy, chronic GC excess is associated not only with mood diseases, but also with cognitive decline, metabolic disorders, diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate affective symptoms, cognitive disturbances, GC and insulin resistance and adverse side effects of conventional drugs through beneficial effects on the hippocampus mitigating its dysfunction and neurodegeneration, neuroinflammation, and impairment of neurogenesis. Since stress/GC-associated neuroinflammation-mediated pathology of the limbic system and, specifically, the hippocampus, is a general feature typical for many brain diseases, the concept of antiGC therapy may be extended, tested and validated in a wider spectrum of cerebral pathologies.



Peculiarities of brain cell functioning during hyperglicemia and diabetes mellitus
Resumo
Hyperglycemia is a symptom and damaging factor of diabetes mellitus (DM) that leads to systemic complications in the body, including macro- and microangiopathies of the brain, impaired blood supply, the appearance of foci of neurodegeneration and might be a trigger of neuroinflammation. Nervous tissue is characterized by a high level of energy consumption and is highly sensitive to fluctuations in the level of metabolic substrates. Therefore, it is extremely important to study the effect of high glucose levels on the functional state of the central nervous system. This review attempts to comprehensively assess the effects of hyperglycemia on brain cells. Analysis of experimental data obtained in in vivo and in vitro models of diabetes on the morphofunctional state of neurons, microglia and astrocytes showed that the direct and indirect effects of glucose in high concentrations depends on the cell type. Receptors and intracellular signaling cascades of astrocytes and microglia, that mediate the effects of hyperglycemia and the development of neuroinflammation, can act as therapeutic targets for the correction for the consequences of diabetes. Thus, finding ways to modulate the functional activity of glial cells may be an effective strategy to reduce the severity of the consequences of CNS damage.



EXPERIMENTAL ARTICLES
Alterations in tissue content of iron and zinc in mice bearing hepatoma 22a and their correction by zinc sulphate supplementation
Resumo
It is known that many tumors induce iron and zinc deficiency in the organism. We studied the content of these metals, as well as the specific activity of two antioxidant metal-dependent enzymes – catalase and superoxide dismutase of three distal organs (thymus, liver and spleen) in animals bearing transplantable hepatoma 22a. These alterations were compared to weight changes of organs. On day 21 of tumor growth, as compared to control group, nonheme iron content in all three organs was decreased, and zinc content – only in the thymus. The specific activities of catalase and superoxide dismutase were both increased in the thymus, while in the liver activity of superoxide dismutase decreased. At the same time point thymic involution and splenomegaly were developed. In order to normalize metal content mice bearing hepatoma 22a were supplemented with 22 mkg of zinc sulphate per ml of drinking water during 3 weeks. Zinc sulphate supplementation partly compensated zinc deficiency in the thymus, increased zinc content in the liver and restored iron content in three organs. It also normalized superoxide dismutase activity in the liver and had no influence on enzymes in other organs. Zinc supplementation did not influence the weight of spleen and liver, but prevented the development of thymic involution. Moreover, metal deficiency in the thymus was restored while the activity of antioxidant enzymes remained unchanged. Based on this we can conclude that thymus involution in hepatoma 22a mice was associated with iron and zinc deficiency in this organ and was not linked with antioxidant enzyme activity, while splenomegaly had no relation to both types of parameters in the spleen. Thus, zinc sulphate positively influences metabolism of two vital trace elements – zinc and iron in animals bearing hepatoma 22a, what contributes to maintaining of the central immune organ – the thymus, and along with this it improves antioxidant system of the liver.



Analysis of correlations between behavioral parameters in the elevated plus maze and the levels of interleukin-1beta in blood plasma in rats
Resumo
Peripheral cytokines may influence psychoemotional behavior, but the role of interleukin-1beta (IL-1beta) in altering anxiety and motor activity in response to inflammatory activation remains unclear. To clarify this issue, correlations between behavioral parameters in the elevated plus maze (EPM) test and plasma levels of IL-1beta after administration of the proinflammatory stimulus lipopolysaccharide (LPS) in different modes were analyzed in adult male rats. LPS in doses of 0.5 or 5 mg/kg, as well as physiological solution (control), were administered to rats intraperitoneally. The most pronounced behavioral effect 24 hours after a single injection was an endotoxin dose-dependent inhibition of the animals’ motor activity. After a dose of 5 mg/kg, increased anxious behavior was also noted every other day. The behavioral changes caused by the high dose of endotoxin were completely normalized after a week. The behavior of the animals one day after the end of repeated injections of LPS at a lower dose for a week (0.5 mg/kg; once every two days) also did not differ from the control. The inhibition of motor activity after LPS could be due to an increase in the level of IL-1beta in the blood plasma, as indicated by the identified significant negative correlations between IL-1beta and the corresponding behavioral parameters. No significant correlation was found between the peripheral level of IL-1beta and such a classic indicator of anxiety as the percentage of entries into the open arms of the maze. In general, the obtained results allow us to conclude that IL-1beta is an undoubted participant in the mechanism of the transient inhibitory effect of LPS on motor activity.



Active avoidance learning in rats with different audiogenic epilepsy proneness
Resumo
The success of the formation of the conditioned reflex reaction of two-way avoidance in the shuttle chamber in rats of 3 strains was evaluated. These were rats predisposed to audiogenic epilepsy – the Krushinsky-Molodkina strain rats (KM), "4" strain (selected from a population of F2 hybrids of the KM strain and sound-insensitive Wistars) and rats of "0" strain, selected for the absence of audiogenic epilepsy from the same population (i. e. these strains, diametrically different in audiogenic epilepsy proneness, possessing a similar genetic background). Experiments have shown significantly more successful assimilation of this skill in rats of the "0" strain.



The relationship of hemorheological blood values and blood velocity of microcirculatory bloodstream in rats` skin vessels
Resumo
Non-invasive study of blood rheology is relevant, but quite complex issue. When systemic blood viscosity and hematocrit levels deviate, blood flow indicators in different parts of microvasculature change. Purpose of the study – research of blood flow characteristics in skin microcirculatory bloodstream of rats obtained by high-frequency ultrasound Dopplerography (HFUD) with given changes in rheological blood indicators. The studies were carried out on pubescent male Wistar rats. 3 experimental groups were formed. Group 1 (n = 21) “Hemodilution” – viscosity 1.99 ± 0.02 mPa*s, hematocrit 31.48 ± 0.31%. Group 2 (n = 32) “Reference values” – animals with unchanged blood levels – viscosity 2.84 ± 0.03 mPa*s, hematocrit 41.60 ± 0.3%. Group 3 (n = 32) “Erythrocytosis” – viscosity 3.95 ± 0.04 mPa*s, hematocrit 54.56 ± 0.23%. Dynamic blood viscosity in vitro studies were carried out on oscillatory viscometer. In order to evaluate hematocrit level heparinized whole blood was centrifuged in glass capillaries using; hematocrit values were assessed taking into account sedimentation of formed elements column using a hematocrit reader card. Blood flow in skin microcirculatory bloodstream of rats` left thigh area was estimated by HFUD method using Minimax-Doppler-K hardware and software system, with ultrasound transducer (frequency 20 MHz). Statistical analysis showed the models are correct. Blood indicators of the animals in three experimental groups differed statistically and significantly in terms of blood viscosity and hematocrit. Discriminant analysis was used to determine the relations between rheological blood parameters and characteristics of blood velocity in microcirculatory bloodstream which made it possible to identify the most significant characteristics of blood flow that tend to change depending on altered blood composition. These include: mean systolic velocity Vas (p < 0.01), mean velocity Vam (p < 0.001), mean volume velocity Qam (p < 0.001), vascular resistance index RI (p < 0.01) and the percentage of blood cells moving in low-speed H' (p = 0.03). The reliability of selected characteristics was checked with one-way analysis of variance; and their significance in determining membership in “Hemodilution”, “Reference values” or “Erythrocytosis” groups according to HFUD data was confirmed. Based on this analysis classification functions were generated for non-invasive dynamic blood viscosity determination according to ultrasound Dopplerography data.



Integration of single-photon miniature fluorescence microscopy and electrophysiological recording methods for in vivo studying hippocampal neuronal activity
Resumo
The miniature single-photon fluorescent microscope (miniscope) enables the visualization of calcium activity in vivo in freely moving laboratory animals, providing the capability to track cellular activity during the investigation of memory formation, learning, sleep, and social interactions. However, the use of calcium sensors for in vivo imaging is limited by their relatively slow (millisecond-scale) kinetics, which complicates the recording of high-frequency spike activity. The integration of methods from single-photon miniature fluorescent microscopy with electrophysiological recording, which possesses microsecond resolution, represents a potential solution to this issue. Such a combination of techniques allows for the simultaneous recording of optical and electrophysiological activity in a single animal in vivo. In this study, a flexible polyimide microelectrode was developed and integrated with the gradient lens of the miniscope. The in vivo tests conducted in this research confirmed that the microelectrode combined with the gradient lens facilitates simultaneous single-photon calcium imaging and local field potential recording in the hippocampus of an adult mouse.



Disturbances of the process of synaptic elimination and its reflection in the wave N170 of auditory evoked potential (AEP) in first psychotic episode of paranoid schizophrenia
Resumo
The reaction of cortical structures of different significance (associated with delusions and hallucination and neutral ones) was studied. The work was conducted in patients with paranoid schizophrenia and normal control (24 patients with paranoid schizophrenia, 15 controls). In patients in frontal areas paradox effect (PE) in AEPs with the increase of both parameters of N170 component was revealed. In central and temporal areas PEs were found in N170 component with the decrease of both parameters of this component. These results point to the “conflict” between the processes of excitation and inhibition in schizophrenia. In schizophrenia patients Pes were revealed in auditory and visual modalities (EVPs and VEPs) on the N170 wave with the unidirectional shifts (increase and decrease) of both parameters in the same cortical areas in AEPs and VEPs. It is supposed that ERP disturbances revealed in patients with schizophrenia are due to the pathology of the synaptic pruning causing the imbalance of excitation-inhibition and leading to the psychosis onset.


