Correction of Disorders in Psychoneurological Status and Functioning of Progenitor Cells of the Nervous Tissue with NF-κB Inhibitor under Conditions of Alzheimer's Disease Modeling.

We studied the effect of NF-κB blockade on the state of various pools of progenitor cells of the nervous tissue and the psychoneurological status of experimental animals with modeled Alzheimer's disease. Administration of scopolamine hydrobromide to C57BL/6 mice for 4 weeks was accompanied by the development of "persistent" disturbances in the orientation and exploratory behavior and mnestic function. An ameliorating effect of the NF-κB inhibitor on these cognitive disorders typical of senile dementia was revealed.

Comparative Study of the Anxiolytic Activity of Songorine in Elevated Plus Maze Test and by Recording Ultrasonic Vocalizations.

It was found that the diterpene alkaloid songorine administered per os to mice at a dose of 25 μg/kg provides a pronounced anxiolytic effect during elevated plus maze testing comparable to the effect of the benzodiazepine anxiolytic phenazepam. Recording of ultrasonic vocalizations of animals revealed an increase in the number of short high-frequency (50 kHz) signals under the action of songorine and the reference drug, which confirms their anti-anxiety properties.

Targeting Adenylate Cyclase: A Novel Concept for Stimulation of Neurogenesis and Pharmacotherapy of Alzheimer's Disease.

Background: The low effectiveness of existing pharmacotherapy strategies for Alzheimer's disease (AD) makes it necessary to develop a new concept for the treatment of this type of dementia. This search is promising to be carried out within the framework of the paradigm of targeting intracellular signaling pathways in Regenerative-Competent Cells (RCCs).

Objective: The purpose of the research is to study the impact of adenylate cyclase (AC) inhibitor on disorders of the psychoemotional status in aged male C57BL/6 mice, as well as on the dynamics of the content and functioning of RCCs nervous tissue.

The Role of Smad3 in the Realization of the Growth Potential of Different Types of Neural Progenitor Cells and the Secretory Function of Neuroglia.

The features of the participation of Smad3 in the functioning of neural stem cells (NSC), neuronal committed precursors (NCP), and neuroglial elements were studied in vitro. It was found that this intracellular signaling molecule enhances the clonogenic and proliferative activities of NCP and inhibits specialization of neuronal precursors. At the same time, Smad3 does not participate in the realization of the growth potential of NSC.

Features of Intracellular Signal Transduction in Neural Stem Cells under the Influence of Alkaloid Songorine, an Agonist of Fibroblast Growth Factor Receptors.

We performed a comparative in vitro study of the involvement of NF-κB, PI3K, cAMP, ERK1/2, p38, JAKs, STAT3, JNK, and p53-dependent intracellular signaling in the functioning of neural stem cells (NSC) under the influence of basic fibroblast growth factor (FGF) and FGF receptor agonist, diterpene alkaloid songorine. The significant differences in FGFR-mediated intracellular signaling in NSC were revealed for these ligands. In both cases, stimulation of progenitor cell proliferation occurs with the participation of NF-κB, PI3K, ERK1/2, JAKs, and STAT3, while JNK and p53, on the contrary, inhibit cell cycle progression.

The Role of JNK and p53 in the Regulation of Secretory Function of Neuroglial Cells of Various Types in β-Amyloid-Induced Neurodegeneration.

We studied the effect of JNK and p53 inhibitors on the production of neurotrophic factors stimulating the realization of the growth potential of neural stem cells by neuroglial cells of various types under conditions of simulation of induced β-amyloid neurodegeneration in vitro. It was shown that β-amyloid stimulates the production of neurotrophins by astrocytes and microglial cells, but does not affect the functioning of oligodendrocytes. JNK and p53 were not involved in the secretion of neurotrophins by intact astrocytes.

The Role of cAMP-Dependent Intracellular Signaling Pathways in the Regulation of the Functions of Neural Stem Cells and Neuroglial Cells in Amyloid-β-Induced Neurodegeneration.

Under conditions of neurodegeneration modeled in vitro by the β-amyloid peptide-(25-35) fragment (Aβ), we studied the role of individual links of cAMP-dependent intracellular signaling pathways in determining the proliferation and differentiation status of neural stem cells (NSCs) and colony-stimulating activity of supernatants from neuroglial cells. The important role of intracellular cAMP and PKA in the inhibition of the progression of the NSC cell cycle and stimulation of the process of their specialization induced by Aβ was found. The selective ability of PKA to block the production of factors constituting colony-stimulating activity by neuroglial cells under conditions of their cultivation in vitro with a neurotoxic agent was revealed.

Participation of cAMP-Mediated Signaling Transduction in the Regulation of the Secretory Function of Neuroglia during Ethanol-Induced Neurodegeneration.

We studied the involvement of cAMP and PKA in the regulation of the secretion of neurotrophic growth factors by macro-and microglial cells in the model of ethanol-induced neurodegeneration in vitro and in vivo. The stimulating role of cAMP in the secretion of neurotrophins by intact astrocytes and oligodendrocytes was shown, while PKA does not participate in this process. On the contrary, the inhibitory role of cAMP (implemented via PKA activation) in the production of neurogenesis stimulators by microglial cells under conditions of optimal vital activity was found.

Functional State of Various Types of Regenerative-Competent Neural Tissue Cells in β-Amyloid-Induced Neurodegeneration.

We analyzed the content and functional activity of various types of regenerative-competent cells of the subventricular zone of the cerebral hemispheres in experimental mice under conditions of in vitro modeling of β-amyloid-induced neurodegeneration. Fundamentally different (opposite) effects of β-amyloid on functional activity of multipotent neural stem cells (NSC) and neuronal committed progenitors (NCP) were revealed. β-Amyloid suppressed proliferation of NSC and stimulated their differentiation.

Psychopharmacological Effects of Stimulation of the Functions of Neural Stem Cells by STAT3 Inhibitor under Conditions of Modeled Ethanol-Induced Encephalopathy.

The psychopharmacological effects of a stimulator of functions of progenitor cells of the nervous tissue STAT3 inhibitor (STAT3 Inhibitor XIV, LLL12) were studied under conditions of modeled alcoholic encephalopathy in C57BL/6 mice. The pharmacological agent corrected the parameters of exploratory behavior (characterizing predominantly cognitive activity) in the experimental animals at the late terms of observation. At the same time, the reproducibility of the conditioned passive avoidance response developed at the beginning of the course STAT3 inhibitor administration decreased.

The Role of MARK ERK1/2 and p38 in Regulation of Functions of Neural Stem Cells and Neuroglia under Conditions of β-Amyloid-Induced Neurodegeneration.

The role of ERK1/2 and p38 in the realization of the growth potential of neural stem cells and secretion of neurotrophic growth factors by glial cells was studied using in vitro model of β-amyloid-induced neurodegeneration. It was shown that amyloid-β fragment 25-35 significantly inhibits the cell cycle progression of neural stem cells against the background of stimulation of their differentiation and reduced production of growth factors by neuroglia. The inhibitory role of ERK1/2 and p38 in relation to the proliferative activity of neural stem cells and the secretory activity of glial elements was revealed.

The Role of JAKs and STAT3 in Regulation of Regenerative-Competent Cells of the Nervous Tissue in β-Amyloid-Induced Neurodegeneration.

We studied the role of JAKs and STAT3 in the growth potential of neural stem cells and the humoral neurotrophic function of neuroglia in modeling β-amyloid-induced neurodegeneration in vitro. It was found that these signaling molecules do not participate in the neural stem cell functioning, and JAKs plays an inhibitory role (realized, however, without STAT3) in the secretion of neurotrophins by glial cells under conditions of their optimal vital activity. The effect of β-amyloid on progenitor cells is accompanied by the appearance of a "negative" effect of STAT3 signaling pathway on their proliferative activity.

Nf-κb: A Target for Synchronizing the Functioning Nervous Tissue Progenitors of Different Types in Alzheimer's Disease.

Background: The efficacy of Alzheimer's disease (AD) treatment can be enhanced by developing neurogenesis regulation approaches by synchronizing regenerative-competent cell (RCCs) activity. As part of the implementation of this direction, the search for drug targets among intracellular signaling molecules is promising.

Objective: This study aims to test the hypothesis that NF-кB inhibitors are able to synchronize the activities of different types RCCs in AD.

The Role of JAK and STAT3 in Regulation of Secretory Function of Neuroglial Cells of Different Types in Ethanol-Induced Neurodegenerationt.

The effects of JAK and STAT3 inhibitors on the production of neurotrophic growth factors by different types of neuroglial cells were studied under conditions of in vitro and in vivo models of ethanol-induced neurodegeneration. It was shown that these signaling molecules do not participate in the secretion of neurotrophins by intact astrocytes and oligodendrocytes. The inhibitory role of JAK in the regulation of this function of microglial cells was revealed.

Mechanisms of the Effects of Short-Term Inhalations of Xe and O Gas Mixture in the Rehabilitation of Post-COVID Ventilation Failure.

The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O gas mixture. Pneumonitis of coronavirus etiology transforms saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film.

A case of xenon inhalation therapy for respiratory failure and neuropsychiatric disorders associated with COVID-19.

Acute respiratory distress syndrome (ARDS) is the main danger to the life of patients with pneumonia caused by SARS-CoV-2. At the same time, respiratory failure (RF) after ARDS can persist for a long time despite intensive therapy. Therefore, it is important to develop new effective approaches for restoring the ventilation function of the lungs after COVID-19.

Role of JNK in the Regulation of Xenobiotic Metabolizing Function of Hepatocytes.

We studied the role of JNK in the regulation of the metabolism of xenobiotic venlafaxine by liver cells under in vitro conditions. The inhibitory role of this protein kinase in the biotransformation of this psychotropic agent by hepatocytes was demonstrated. JNK inhibitor added to the liver homogenate containing antidepressant enhanced and accelerated the formation of the only pharmacologically active venlafaxine metabolite O-desmethylvenlafaxine in the cell suspension.

Role of MAPK ERK1/2 and p38 in the Regulation of Secretory Functions of Different Populations of Neuroglia in Ethanol-Induced Neurodegeneration.

We studied the participation of ERK1/2 and p38 in secretion of neurotrophic growth factors by various types of neuroglia under conditions of in vitro and in vivo modeled ethanol-induced neurodegeneration. The inhibitory role of these protein kinases in the production of neurotrophins by intact astrocytes and the absence of their participation in the regulation of functions of oligodendrocytes and microglial cells were shown. Under conditions of ethanol neurotoxicity, the role of ERK1/2 and p38 in the production of growth factors by glial elements was significantly changed.

The Role of Intracellular Signaling Molecules in the Production of Granulocytic CSF Mononuclear Phagocytes in Stress and Cytostatic Influence.

Under conditions of steady-state hemopoiesis, nuclear factor NF-κB, in contrast to MAP kinase p38, plays an important role in the maintenance of the initial level of secretory activity of monocytes. The increase in the production of G-CSF under stress conditions (10-h immobilization) is mainly regulated by the alternative p38MARK signaling pathway via activation of p38 synthesis. It was shown that under conditions of cytostatic-induced myelosuppression, the production of protein kinase p38 in cells decreases, and it, like NF-κB, is not the main one in the production of hemopoietin by mononuclear phagocytes.

Targeting cAMP-pathway in Regeneration-competent Cells of Nervous Tissue: Potential to Create a Novel Drug for Treatment of Ethanol-induced Neurodegeneration.

Background: Existing neuroprotective drugs are not effective enough to treat alcoholic encephalopathy. This makes the development of novel pharmacological approaches to treating patients with ethanol-induced neurodegeneration(EIN) relevant. Therefore, the search for new targets among intracellular signaling molecules of regeneration-competent cells of nervous tissue is promising.

Role of JNK and p53 in Implementation of Functions of Various Types of Regeneration-Competent Cells of the Nervous Tissue.

We studied the participation of JNK and p53 in the realization of the growth potential of different types of progenitors of the subventricular zone of mouse brain and secretion of neurotrophins by glial cells. The stimulating role of these signaling molecules in mitotic activity and specialization of multipotent neural stem cells was shown. It was found that JNK and p53 do not participate in the regulation of committed neuronal progenitor cells (clonogenic PSA-NCAM cells).

Erythropoesis-Stimulating Properties of Anthocyanin-Containing Complexes in Cytostatic Anemic Syndrome.

We studied the effect of an anthocyanin-containing complex from Sorbus aucuparia L. on the main indicators of erythropoiesis in the blood and bone marrow of mice against the background of doxorubicin treatment. It was shown that administration of an anthocyanincontaining complex from S.

Specific Features of Intracellular Signal Transduction in the Regulation of Functions of Neural Stem Cells and Committed Neuronal Progenitors.

We studied the role of NF-κB-, cAMP/PKA-, JAKs/STAT3-, ERK1/2-, p38-, JNK- and p53- mediated signaling pathways in the realization of the growth potential of neural stem cells and committed neuronal progenitors under in vitro conditions. The method of pharmacological blockade with selective inhibitors of individual signaling molecules revealed some principal differences in their role in the determination of the proliferation and differentiation status of progenitor cells of different classes. Analysis of the peculiarities of intracellular signaling in cells and comparison of the role of its individual elements attest to the prospects of developing new drugs with neuroregenerative activity based on STAT3 inhibitors or JNK activators.

Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration.

Objectives: The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising. We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration and .

Methods: , the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled and was studied.