卷 110, 编号 9 (2024)

The study of peripheral nervous system glial cells is an actual problem of modern neurobiology. The purpose of this work was to summarize our own and published data on the distribution of glial fibrillary acidic protein (GFAP) in peripheral nervous system (PNS) glial cells. The features of GFAP expression in glial cells of the enteric nervous system, dorsal root ganglion and peripheral nerve were examined. A comparative study of different populations of PNS gliocytes led to the conclusion that the intermediate filament protein GFAP is distributed differently in them. Analysis of the literature showed that despite the fact that this protein is widely used as a molecular marker of glial activation, there is still no understanding of the exact mechanisms of GFAP participation in the glial reactive response. The described features of GFAP+gliocytes from different parts of the PNS demonstrate the functional polymorphism of this protein. Its ability to be expressed in peripheral nervous system gliocytes in response to injury requires further research.

The prefrontal cortex (PFC) plays a key role in cognitive plasticity and is involved in various processes of higher nervous activity. At the same time, studying the processes underlying various forms of behavior in which PFC neurons participate is a non-trivial task. The associative functions of the PFC are associated with the nature of the connectivity of this structure with other areas of the brain, which, according to recent data, is much more complex than previously thought. Thus, it becomes clear that the axons of PFC projection neurons have many collaterals projecting to many different targets in the brain. In this review, we highlight the latest results in studying the connectivity of PFC neurons using the latest methods for analyzing projections and single-cell transcriptomes. Brain-derived neurotrophic factor (BDNF) plays an important role in the functioning of these neurons and their projection targets, but the transport of this neurotrophin by PFC projection neurons to structures where it is not locally expressed may be especially important. We review recent results mapping such neurons in the PFC, highlighting Bdnf expression and potential role in the pathogenesis of mental disorders.

The electromyographic activity of the soleus muscle is a reliable indicator of its functional status. Unloading of support causes an immediate cessation of electrical activity in the soleus muscle, which resumes upon restoration of the support load. Prolonged support unloading, however, results in the emergence of spontaneous electrical activity in the soleus muscle. Previous research has established a correlation between this activity and the presence of the potassium-chloride cotransporter (KCC2) on the membranes of spinal cord motor neurons. Additionally, it has been demonstrated that the introduction of the KCC2 activator prochlorperazine can eliminate spontaneous muscle activity. This study aimed to investigate the impact of CLP290, an alternative KCC2 activator, on the spontaneous tonic activity of the rat soleus muscle. The results indicated that daily administration of CLP290 to rats during a 14-day period of hindlimb suspension prevented the reduction in KCC2 levels in the motor neurons of the lumbar spinal cord and the increase in spontaneous tonic activity in the soleus muscle. Notably, there were no significant differences in the cross-sectional area of slow-type fibers between the antiorthostatic suspension groups with and without CLP290 administration.

The work examined the expression of apoptosis, autophagy and necroptosis markers in hippocampal cells of rats after long-term consumption of excessive F^- doses at the transcriptional and translational levels. Male Wistar rats were divided into 4 groups receiving 0.4 (control), 5, 20 and 50 mg/l F^- (as NaF) for 12 months. The changes in contents of effectors of mitochondrial (Bcl-2, Bax, Caspase-9, Caspase-3) and receptor (Caspase-8, Fas) pathways of apoptosis, mediators (Ulk-1, Beclin-1) and modulators (AMPK, Ark, mTOR) of autophagy, as well as that of necroptosis (RIP and MLKL) were assessed by immunoblotting, the gene expression (Bcl2, Bax, Casp3, Ulk1, Beclin1, Prkaa1, Akt, and mTor) – by real-time PCR. In the hippocampus of F – exposed animals, the expression ratio of Bcl2/Bax genes and Bcl-2/Bax proteins decreased, caspase-9 and caspase-3 were activated, but the level of caspase-8 and membrane Fas receptor remained stable. Long-term F^- consumption had no effect on the content of autophagy initiator Ulk-1 and protein kinases AMPK, Akt and mTOR, but resulted in inhibition of key autophagy mediator Beclin-1. The expression level of necroptosis RIP and MLKL effectors in the hippocampal cells of rats received excessive F^- did not change as well. Thus, long-term F- exposure was accompanied by activation of apoptosis, mainly through the mitochondrial pathway, at the background of autophagy suppression.

IP3 receptors are found in significant quantities in muscle fibers in the sarcoplasmic reticulum, nucleus and mitochondria. We hypothesized that activation of IP3 receptors (IP3Rs) during muscle unloading may induce a weak calcium release signal, both cytosolic and nucleoplasmic, that promotes (possibly with other signaling cascades) the activation of transcription factors, leading to the expression or repression of genes involved in muscle phenotype. This hypothesis was tested by blocking IP3R during unloading of rat muscles by administering 2-APB (2-aminoethoxydiphenyl borate). Wistar rats were administered intraperitoneally at a dose of 10 mg/mg in 5 % DMSO daily. We found that the IP3R state influences the development of atrophic processes in the postural m. soleus during unloading. Administration of the IP3R blocker 2-APB to animals successfully prevented a decrease in m. soleus cross-sectional area (CSA) of both fast and slow muscle fibers. The slowdown in CSA decrease upon administration IP3R inhibitor during 7 days m. soleus unloading is associated with the prevention of a decrease in ribosomal biogenesis and an increase in the expression of autophagy markers ULK-1 and IL-6.

Increased viscosity of whole blood can make a significant contribution to an increase in total peripheral resistance, disruption of systemic hemodynamics and microcirculation disorders in arterial hypertension. However, changes in blood viscosity (BV) also lead to changes in shear stress on the endothelium, which can affect vascular tone. There have been no studies of the relationship between changes in BV and blood pressure in animals under conditions of arterial hypertension. The purpose of the work was to study the correlation between blood viscosity and blood pressure in normotensive Wistar rats and spontaneously hypertensive rats (SHR) under normal conditions, as well as under conditions of decreased and increased blood viscosity. Reduction/increase of BV was carried out using isovolumic hemodilution/hemoconcentration. Mean arterial pressure (MAP) was recorded using the MP150 system (Biopac Systems, Inc, USA). BV was measured on a Brookfield DV–II+Pro rotational viscometer (Brookfield Engineering Labs Inc., USA) at a shear rate of 450 s^-1. In normotensive rats there were no statistically significant correlations between the initial values of BV and MAP. After isovolumic hemodilution or hemoconcentration in normotensive rats, statistically significant correlations between BV and MAP were also not found. In SHR, compared with Wistar rats, a significant positive statistical relationship of moderate strength was observed between the initial values of BV and MAP (R = 0.643, p < 0.05). In SHR, the identified statistically significant correlations of moderate strength between the values of BV and MAP remained, both after hemodilution (R = 0.530, p < 0.05) and after hemoconcentration (R = 0.689, p < 0.05). Analysis of correlations shows that in SHR, unlike Wistar rats, changes in blood pressure passively follow changes in blood viscosity, which is probably due to the failure of the mechanisms of endothelium-dependent vasodilation in hypertension.

One of the informative and widely used approaches to understanding the pathogenetic (including neurobiological) mechanisms of schizophrenia is the study of patients with clinically high risk (CHR) for the disease. The power and topography of the theta rhythm event-related synchronization (ERS) related to peripheral stimulus that must be remembered (memory-guided saccades/antisaccades paradigm) have been studied in the groups of 20 mentally healthy subjects and 20 patients with CHR. The analysis was carried out according to the Pfurtscheller method. Based on the saccades latency value and the error numbers, the task performance was decreased in patients with CHR compared to healthy subjects. Intergroup differences by theta rhythm ERS magnitude and topography were found for three consecutive delay period intervals (900 ms each) before saccades to the right and antisaccades to the left. The findings are considered as being the reflection of violations of the spatial attention and working memory maintaining in CHR patients that has a certain interhemispheric asymmetry. It has been suggested an activation of the compensatory processes and the cognitive control reorganization of the fronto-parietal networks with predominantly right hemisphere preservation at the early stage of schizophrenia development.

P2X3-receptors localized in the hippocampus participate in the transmission of excitation and the formation of synaptic plasticity underlying learning and memory. P2X3-receptors are of great importance in the occurrence of neuropathic pain in epilepsy, acute and inflammatory pain of various genesis and localization as well as in the activation and growth of nerves after traumatic brain injury. The aim of the study was to study the elastic properties of the surface and the metabolic profile of neurons in an embryonic primary mixed hippocampal culture under P2X3-receptor blockade. The study was performed on a primary mixed culture of hippocampal neurons obtained from CD1 mice on the 18th day of gestation (E18). The highly selective blocker 5-(5-iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2.4-diamine monochloride salt was selected as a P2X3-receptor blocker. To assess the elastic properties of neurons Young's modulus that characterizes the rigidity of the cell surface was measured. Measurements on an atomic force microscope applying a load in 25 local areas of the cell surface were performed. At each point, the force curves of the cantilever approach and retraction were recorded with subsequent calculation of Young's modulus. The metabolic profile of the neuroglial culture in Energy Phenotype test on a Seahorse HS mini cell metabolism analyzer (USA) was studied. The Young's modulus of the cell surface of neurons in the control was in the range from 6.8 ± 0.1 to 9.7 ± 0.2 kPa, and under the action of the P2X3-receptor blocker in the range from 3.1 ± 0.1 kPa to 8.5 ± 0.1 kPa. Under the conditions of P2X3-receptor blockade on the 5th day of differentiation the Young's modulus of the cell surface was reduced by 62% (p < 0.05), on the 8th day it increased by 22% (p < 0.05) and by the 11th day it decreased by 16.7% (p < 0.05) compared to the control. Aerobic respiration was characteristic of the embryonic hippocampal culture both in the control and with the P2X3-receptor blockade. Consequently, the blockade of the P2X3-receptor did not affect the metabolic profile of the E18 hippocampal culture. The obtained data indicate the direct participation of the P2X3-receptor in the formation of biomechanical properties of the cell surface in the processes of differentiation and signal transduction. It is possible, that the blockade of the P2X3-receptor will be one of the promising molecular targets that can reduce neuronal damage in brain injuries, neuroinflammation, hypoxia, and epilepsy. In addition, the study of the P2X3-receptor blockade can expand the fundamental understanding of the role of the purinergic signaling system in the formation of complex neuronal morphology at early stages of embryonic development under conditions of rapid excitatory signal transmission mediated by the ATP molecule.

The results we obtained earlier indicate the potential for corrective effects on the negative consequences of social isolation on the functioning of the body through an enriched environment. The aim of the present study was to investigate the influence of housing conditions for rats – standard conditions, social isolation, and an enriched environment – on the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis, focusing on HPA axis stress reactivity, pain sensitivity, and rat behavior following exposure to an ulcerogenic stressor. The experiments were conducted on male Sprague-Dawley rats. Thirty-day-old rats, after being weaned from their mothers, were placed in different housing conditions for four weeks: standard environment (SE), isolation (SI), or an enriched environment (EE). After four weeks, rats from each group were exposed to an ulcerogenic stressor (US): 3 hours of cold immobilization (10 °C). Starting the day after US exposure, for one week, all groups of rats were sequentially assessed for somatic pain sensitivity (in the “hot plate” test), behavior (in the “open field” and “elevated plus maze” tests), and HPA stress reactivity (based on corticosterone levels in response to mild procedural stress). According to the results, SI conditions in our experimental setup led to a faster increase in body weight with age, higher anxiety levels, depressive-like reactions in half of the animals studied, and increased sensitivity to painful stimuli. At the same time, rats kept in the EE showed higher HPA axis stress reactivity, greater motor and exploratory activity, lower anxiety, and lower sensitivity to painful stimuli. The obtained results provide new evidence supporting our previous conclusion that SI exerts maladaptive effects on the overall functional state of the rats' bodies, while EE, on the contrary, leads to adaptive changes in the body. This study highlights the importance of an integrative approach when studying the effects of SI and EE on the body.