The treatment of various types of dementia remains a challenging task for psychiatry and neurobiology. This group of diseases is characterized by progressive impairment of cognitive functions and memory, accompanied by neurodegenerative processes in different areas of the brain. Drug treatment does not halt the degeneration of nervous tissue. Cell therapy using neural stem/progenitor cells is considered a promising approach for the treatment of various types of dementia. This paper discusses the unique properties and possible mechanisms of the influence of these cells after transplantation on the regeneration of nervous tissue, as well as specific examples of using the neural stem/progenitor cells from various sources in different types of dementia. Based on the analyzed data, it can be concluded that the olfactory mucosa might be a promising and accessible source for the creation of autologous cell-based preparation. Therefore, further research is needed on the use of olfactory mucosal neural stem/progenitor cells in the context of dementia.
Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by deficits in social interaction, stereotypic behavior, and restricted interests. In ASD, dysregulation of proteins associated with synaptic plasticity, particularly brain-derived neurotrophic factor (BDNF), as well as elevated levels of inflammation, are observed. Investigating the involvement of BDNF in the pathogenesis of ASD and the search for new therapeutic agents represent an important task in psychopharmacology. The aim of this study was to investigate the effects of the low-molecular-weight dipeptide BDNF mimetic hexamethylenediamide bis(N-monosuccinyl-L-seryl-L-lysine) (GSB-106) on behavioral features and inflammation in rats with experimental ASD. ASD was modeled by administering valproic acid (VPA) at a dose of 600 mg/kg to female Wistar rats on gestational day 12.5. The offspring (both males and females) received GSB-106 orally at a dose of 0.1 mg/kg daily from postnatal day 7 (P7) to P81. From P39 to P81, stereotypic behavior, exploratory and locomotor activity, and pain sensitivity were assessed, followed by evaluation of inflammation by measuring complement system activity and the content of multiple-modified low-density lipoproteins (mmLDL). GSB-106 at a dose of 0.1 mg/kg reduced stereotypy 2.0-fold (p < 0.05), increased exploratory activity 1.3-fold (p < 0.05), and improved locomotor coordination 1.5-fold (p < 0.05) in male rats with ASD compared to the VPA group. In female rats with ASD, GSB-106 increased the pain threshold 1.2-fold (p < 0.05) and improved locomotor coordination 1.9-fold (p < 0.001). The effect of GSB-106 on metabolic and oxidative processes associated with inflammation was observed only in male rats with experimental ASD, as evidenced by a 39.9
Pregnancy in mammals is accompanied by deep restructuring of the cardiovascular system to provide adequate blood supply to the fetus and to maintain maternal homeostasis, where blood pressure and heart rate variability serve as important indicators of the system’s state and the effectiveness of its regulation mechanisms. The study investigated changes in hemodynamic parameters in pregnant and non-pregnant rats in response to acute hypoxic stress, experienced at different periods of gestation. It was shown that normal pregnancy is accompanied by a physiological decrease in blood pressure and a restructuring of autonomic regulation with activation of the sympathetic branch and a decrease in parasympathetic activity with a stable heart rate. Hypoxia in early pregnancy caused a significant and prolonged decrease in blood pressure, while in late gestation there were no blood pressure changes in response to the lack of oxygen but bradycardia persisted in both cases. Moreover, females exposed to hypoxia in late gestation demonstrated increased heart rate variability with activation of the parasympathetic system the following day. The dysregulation observed could cause long-term consequences, increasing the risk of cardiovascular diseases and impairing the adaptive potential of the mother’s body.
Due to the growing pollution of the environment with a microplastic (MP), the problem of MP impact on human health is relevant. MP is considered to contribute to the development of inflammatory bowel diseases. Therefore, we assessed the effect of long-term MP consumption on the expression of genes associated with the colon barrier function and on the luminal microflora composition in healthy mice and in mice with acute colitis. The effect of MP was modeled by replacing drinking water with a 10 mg/L suspension of 5 µm polystyrene particles for six weeks. To model acute colitis, 1
Metabolic syndrome (MS), a global problem of the 21st century, is characterized by hypertension, which is caused by the predominance of vasoconstriction over vasodilation. Hydrogen sulfide (H2S) is a recognized endogenous gas signaling molecule that has a variety of biological effects, including changes in vascular tone. The aim of this work was to study changes in contractile activity in isolated rat aorta in response to sodium hydrosulfide (NaHS), an H2S donor, and endogenous H2S during metabolic disturbances induced by a high-calorie (Western) diet. The study was performed on mature male Wistar rats. The diet resulted in the development of metabolic disturbances typical for MS. The results of a myographic study of thoracic aortic segments indicated that, in both the control and experimental groups, the administration of NaHS, depending on its concentration, resulted in bimodal effects, causing vasoconstriction at low concentrations and significantly more pronounced vasodilation at high concentrations. The effect of endogenous H2S depends on the state of perivascular adipose tissue and decreases in MS. Thus, the increase in H2S-induced vasodilation in MS is likely reflects a compensatory response to a decrease in endogenous H2S production. ATP-sensitive potassium channels play a leading role in mediating relaxation responses of aortic smooth muscle to H2S. However, their contribution to the development of vasodilation is less pronounced in MS, which is a consequence of changes in the involvement of other mechanisms. A decrease in H2S-induced vasoconstriction in MS, caused by increased superoxide anion production, may be one of these mechanisms. The interaction of various pathways for the implementation of H2S-induced vasorelaxation in metabolic disorders represents an important direction for further research to prevent the development of vascular diseases, including by regulating vascular tone.
Epilepsy is often accompanied by psycho-emotional disorders, the most common of which are anxiety disorders, depression and conditions leading to impaired social interaction. This study investigates the social behavior of rats with different predispositions to audiogenic epilepsy: Krushinsky-Molodkina (KM) rats with high sensitivity to sound and “0” rats selected from a population of F2 hybrids of the KM rats and Wistar rats, insensitive to sound stimulation, for the absence of audiogenic epilepsy. The results demonstrate social behavior impairments in both intact “0” rats and intact KM rats. The “0” rats in the social tests showed interest in social stimuli but did not prefer the new stimulus to the old one, while the KM rats showed no social preference, nor interest in social novelty. After repeated sound stimulation (audiogenic kindling), KM rats developed myoclonic seizures, paralleled by aggravation of social deficits, while the social behavior of “0” rats, resistant to the seizure provocations, did not significantly change.
A new strain of the unicellular green microalga Micractinium thermotolerans VKM Al-430 (Trebouxiophyceae, Chlorophyta) was isolated from a technogenically polluted reservoir. Its taxonomic affiliation was determined by analyzing the sequences of internal transcribed spacer regions ITS1 and ITS2 and by comparing their secondary structures with those of the authentic strain M. thermotolerans VKM Al-332. In a series of intensive-cultivation experiments in a modern photobioreactor under elevated carbon dioxide concentration (up to 5
Under certain conditions, fungi can rapidly change the size of their cells. For example, it is known that cells of many yeast species under hyperosmosis instantly and reversibly shrink entirely, without plasmolysis, with a decrease in volume of up to 70
Tobacco mild green mosaic virus (TMGMV, genus Tobamovirus, family Virgaviridae) was detected for the first time on a new host plant, the peony Paeonia wittmanniana Hartwiss ex Lindl. The virus was found in the Botanical Garden of Moscow State University when studying the virome of a peony plant with wrinkling symptoms on the leaves using high-throughput sequencing. A virus-specific contig with a length of 6331 nucleotides was assembled. It represented a nearly complete sequence of the TMGMV genome, contained four open reading frames typical of tobamoviruses, and was most closely related (99.2
An important task on the way to creating a competent cellular equivalent of a biological heart pacemaker for the treatment of cardiovascular diseases is to assess the ability of cultured cardiomyocytes in conglomerates, layers, or pseudo-tissues to automatic, spontaneous activity. It is known that the electrophysiological and tissue properties of cultured cardiomyocyte structures differ significantly from native ones. In this work, based on a comparison of the transcription profile and an assessment of the expression level of key genes in the tissues of the sinoatrial node (SAN), atrium, neonatal cardiomyocytes, and cultured cardiomyocyte conglomerates of rats, pacemaker competence indices (PCI) are proposed, characterizing the ability (competence) of cellular structures to function as a pacemaker. Based on the analysis of mRNA sequencing data, it was found that there is a significant change in the expression profile of functionally significant genes during neonatal cardiomyocytes’ cultivation, which enhances the difference in the phenotype of emerging cardiomyocyte conglomerates from both the pacemaker of SAN and the contractile myocardium. It has been shown for the first time that satisfactory PCIs can be obtained based on an assessment of the transcript level of no more than four genes, including pairs of transcription factors (Tbx3, Tbx18 and Nkx2.5, Gata4) or pairs of ion channels (Hcn4, Kcnj2) and gap junctions (Gjc1, Gja1) antagonistically expressed in the SAN and contractile myocardium. The PCI simplifies and accelerates the assessment of the functional properties of artificial spontaneously active cardiomyocyte cell structures.
This opinion article examines the functional heterogeneity of cells composing adipose tissue (AT) and the potential for cross-species comparisons of single-cell transcriptomic analysis results using rodents as an example. Metabolic syndrome and obesity are closely related. In turn, obesity-associated AT dysfunction is accompanied by changes in cell composition of AT. The development of single-cell transcriptomic analysis methods in recent years, particularly snRNA-seq, and their popularization have provided a particularly powerful tool for studying the heterogeneity of AT cell composition. Animal models such as murine ones are widely used to study various aspects of AT biology; however, translating these findings to humans can be complicated by interspecies differences in the anatomy and cell composition of the tissue. This article summarizes some of the most important results of studying AT heterogeneity in humans and mice using such methods. To date, a number of functional subpopulations of both mature adipocytes and stromal-vascular fraction cells involved in their turnover are known. There is limited data in the literature on adipocyte subtypes and stromal-vascular fraction cells characterized by some comparability between humans and mice in terms of marker gene expression and obesity-induced changes. However, little data published to date on AT heterogeneity does not allow one to draw full conclusions on the interspecies comparability of AT cell subpopulation composition. This underscores the importance of a more detailed study of various aspects of AT cell heterogeneity.
Drawing on many years of experience in editing for biomedical journals and lecturing on scientific article formatting for PhD students at Moscow State University, the author analyzes the current state of statistical analysis of biological, biomedical, and medical research results, in particular, data obtained in studies aimed at discovering drugs that supposedly slow aging and suppress the development of age-related diseases. He emphasizes that, in many cases, such analysis is either not performed at all or is performed incorrectly. Authors often analyze data that does not follow a normal distribution using the parametric Student’s t-test. Moreover, many researchers, having failed to obtain reliable results (p > 0.05), are increasingly replacing the term “significance” in their articles with “trend,” which seems completely unacceptable. Although this problem affects not only biomedical but also other natural science research, it is especially important for biomedicine, as it is at stake in human life and health. It is proposed that greater attention should be paid to this issue by both reviewers of relevant articles and editors of the journals in which they are published. Furthermore, the importance of teaching the basics of statistical processing of research results to undergraduate and graduate students in biological, biomedical, and medical institutes, as well as relevant university schools, is emphasized.
The use of molecular phylogenetic methods has caused a profound rearrangement of the system and phylogeny of the triploblastic Bilateria (=Triploblastica). Nevertheless, in most phylogenetic trees, two main clades remain, coinciding with Protostomia and Deuterostomia, established by K. Grobben (1908) more than 100 years ago. For both clades of Triploblastica, amphystomy is the primary way of forming a through gut. However, the analysis shows that only the origin of the mouth and anus does not allow us to distinguish between the two main clades. All the groups that were referred to Grobben’s Protostomia are characterized by an ectodermal pharynx, therefore this clade would be more correctly called Ectopharyngeata. Based on the modification of the pharyngeal cuticle, many ectopharyngeates develop various structures designed to grind food. The groups attributed by Grobben to Deuterostomia have an endodermal pharynx, therefore it would be more correct to call this clade Endopharyngeata. The synapomorphy of Endopharyngeata is the development of gill slits in the walls of the endodermal pharynx and the division of the pharynx into two zones: the dorsal branchial zone and the ventral digestive zone. During the evolution of the chordates, the sides of the body were inverted. As a result, the part of the digestive tube that is homologous to the hemichordate digestive zone of the pharynx became the dorsal notochord and the branchial zone of the pharynx turned out to be ventral. Thus, the division of Triploblastica into two clades entirely retains its significance in modern biology, although it is based on a different set of morphological features than that considered by Grobben.
Myrtus communis L. (common myrtle) is one of the important aromatic and medicinal plants of the family Myrtaceae. Its organs contain sufficient quantities of essential oils, phenolic acids, flavonoids, tannins, anthocyanin pigments, and fatty acids, which make it a promising object for the pharmaceutical and perfume industries. In the Russian Federation, M. communis has been cultivated as an ornamental and essential oil plant on the Southern Coast of Crimea and the Black Sea coast of the Caucasus since the 19th century. In the conditions of the Southern Coast of Crimea, M. communis leaf blade and fruit morpho-anatomical characteristics were investigated. However, data on the stem structure is still limited overall. Therefore, the aims of this work were a comparative analysis of the non-woody (young) and woody stem anatomy and the detection of the localization of essential oil and phenolic compounds in its tissues. It was estimated that the young and woody stems of M. communis differed in color and shape, and a possible contribution of the axial organs to a whole portion of the essential oil yield was determined. It was shown for the first time that the woody stems of M. communis had a special type of phellem cells that were elongated in the radial direction with thin cell walls. The special structure of the secondary dermal tissue may cause freezing of shoots and limit the spread of M. communis beyond the humid and dry subtropics of the Russian Federation. Qualitative histochemical studies revealed accumulation of essential oil in the cavities of young and woody stems, with suberization of the endogenous secretory structure sheath layer cells and a tendency for their destruction as the periderm develops. Phenolic compounds are found in stem tissues, some of which are structurally linked to cell walls, while others accumulate in the protoplasts of the epidermis, parenchyma, and phloem, and the greatest quantities are in young (non-woody) organs.
The content of vitamins in the body is one of the most important indicators reflecting the level of nutrition of large ungulate mammals living on the northern periphery of their range in conditions of limited access to food resources in the cold period of the year. In this work, the content of retinol (vitamin A) and α-tocopherol (vitamin E) in the organs and tissues of wild moose (Alces alces) of different ages and sexes, as well as European red deer (Cervus elaphus) and maral (C. e. sibiricus) kept in semi-free conditions in the Northwest of Russia (Republic of Karelia and Leningrad Region) was studied. Biological material was collected from animals harvested because of legal hunting during the hunting season from October to January. The level of vitamins in the studied animals was generally consistent with the values established for cervids living in other regions of the world, including those with a milder climate. Relatively low vitamin content identified in species of the genus Cervus warrants further investigation. In moose, no sex- or age-related differences were found in the content of vitamins A and E, except for a lower level of α-tocopherol in the kidneys of adult females compared to young ones. Pregnant females had a comparatively low retinol content in the examined organs and tissues. The effect of the region in which the moose were hunted on the content of retinol in the liver and α-tocopherol in the heart was found, which may be due to the natural and climatic features of the study areas, which determine the composition of phytocenoses and the forage nutritive value. The results obtained can be used to assess the status of large ungulates and their population level management plans.
The extracellular matrix (ECM) synthesized by multipotent mesenchymal stromal cells (MSCs) plays a critical role in regulating the cellular microenvironment and is widely used in the development of biomaterials for regenerative medicine. The present study demonstrated the influence of cell culture conditions on ECM collagenous compartments secreted by umbilical cord-derived MSCs (MSCs-UC), including the geometric parameters, structure complexity, and production of collagenous proteins. The effects of gelatin coating, cell culture duration, fetal bovine serum concentration, and ECM-stimulating supplements (sodium 2-phospho-L-ascorbate and carrageenan) were examined. The optimized protocol included cultivation of MSCs-UC on gelatin-coated plates for 11 days in α-MEM supplemented with 10
The structure of the gp56 axial fibril forming part of the adsorption apparatus of the phi24B Stx-converting phage was studied using cryo-electron microscopy. The axial fibril is highly mobile, and the gp56 trimer is surrounded by the massive complex of the gp57 nozzle protein hexamer, which creates a symmetry mismatch at the interface and makes it difficult to obtain a three-dimensional reconstruction. Using the symmetry expansion approach and local refinement, we have generated a density map of the axial fibril, visualized the tertiary structure of its globular domains, and determined their location relative to the other proteins of the phi24B adsorption apparatus.
The data of modern neurobiology indicates a critical dependence of the nervous system formation upon the conditions of intrauterine development. Pregnancy, childbirth and the early postnatal period are of key importance for normal maturation of the nervous system. The developing fetus is especially vulnerable to the effects of adverse external and internal factors in periods of brain and neuronal structures’ morphological differentiation, during childbirth, and the transition to independent breathing. Fetal and/or newborn hypoxia is considered one of the main causes of disorders in brain development, manifested later in the form of cognitive impairments, problems with learning, memory and attention, social interactions, movements, and emotions. The aim of the present study was to investigate the effect of prenatal hypoxia, suffered in periods critical for brain development and maturation, on the ability of white rats for motor and spatial learning. It was shown that males that survived acute late gestational hypoxia turned out to be more sensitive to its effects, demonstrating at the age of 1 month both a deficit in learning, reproduction and maintainance of motor skills, and a failure in solving a cognitive task in a T-shaped maze. At the same time, acute hypoxia of the early organogenesis period had hardly any effect on the ability of peripubertal animals for motor and spatial learning. Therefore, comprehensive testing allows one to assess the effects of hypoxic brain damage more completely, which is important for early diagnosis and the development of rehabilitation programs.
This article presents the results of a study into the species diversity of representatives of the clade Chlorella in Lake Otstoynik (Tolyatti, Samara oblast). This reservoir was used until 1996 for the disposal of nitrogen-tuck production waste but is currently at the stage of self-healing. In the course of the work, 15 strains of microalgae with Chlorella-like morphology were studied. Based on the results of molecular genetic analysis using the internal transcribed spacers ITS1 and ITS2, it was found that only three strains were true representatives of the genus Chlorella. Microalgae from the genera Brachionococcus, Lobosphaeropsis, Micractinium, and Meyerella were also found. In addition, two strains belonged to species that are still formally classified as Chlorella, but their actual taxonomic status needs to be clarified. This study has once again clearly shown that valid identification of Chlorella-like microalgae is not possible using only light microscopy methods. Methods of molecular genetic analysis must be used to study the true species’ richness.
A comparative study of characteristics of the auditory sensitivity in intact Wistar rats and heterozygous rats of transgenic DAT-HET line (dopamine transporter heterozygous) rats with reduced expression level of the Slc6a3 gene encoding the dopamine transporter 1 (DAT-1) was conducted; they represent an experimental model of dopaminergic neuron system pathology (attention deficit hyperactivity disorder). During the study, the amplitude and temporal parameters of auditory brainstem responses (recorded from the rats of both lines under presentation of paired clicks and single tones) were analyzed. The characteristics of auditory sensitivity of Wistar and DAT-HET rats were similar, but a comparative analysis of the wave amplitudes of auditory brainstem responses revealed a significantly larger amplitude of wave 1 in DAT-HET rats. Data obtained suggest that DAT-HET heterozygotes differ from rats with normally functioning dopamine transporter DAT-1 by an increased level of dopaminergic signaling associated with the activation of D1 receptors localized in the membranes of the cochlea spiral ganglion neurons.
