Rossijskij fiziologičeskij žurnal im. I.M. Sečenova

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by the loss of dopaminergic neurons and the accumulation of aggregated alpha-synuclein protein. The molecular mechanisms underlying PD pathogenesis remain largely unknown, and as a result, no effective neuroprotective therapies are currently available. However, recent research has identified a link between alpha-synuclein accumulation and aggregation, activation of type I interferon responses in microglia, and subsequent neurodegeneration. STING (Stimulator of Interferon Genes) is a key regulator of innate immunity, responsible for the production of type I interferons and the orchestration of inflammatory responses. Upon activation, STING initiates signaling cascades that regulate immune responses, cell death mechanisms, and autophagy. In the context of PD, STING hyperactivation may contribute to the progression of neuroinflammation and associated neurodegeneration. Therefore, the development of STING inhibitors capable of modulating its activity is considered a promising therapeutic strategy for PD. At the same time, due to the multifunctional roles of STING in cellular processes, therapeutic approaches targeting STING in PD must carefully balance its activity and therapeutic efficacy. This balance may be achieved through combinatory treatments involving STING inhibitors and compounds that reduce alpha-synuclein levels. This review discusses the structural features and activation mechanisms of STING, its role in the regulation of cell death and autophagy, as well as potential therapeutic strategies targeting this pathway for the development of novel treatments for PD–particularly PD associated with mutations in the GBA1 gene.

Progesterone plays a major role in preparing the female body for and maintaining pregnancy. Classical nuclear progesterone receptors (nPRs) have been found in the female reproductive organs, through interaction with which progesterone exerts multiple effects in these tissues. Recently, membrane progesterone receptors (mPRs) have also been found in the uterus, placenta, ovaries, and mammary glands of humans and animals. It is assumed that these receptors fulfil important functions in the maintenance of pregnancy, in the initiation of labour. However, their role in these processes has not been studied. Earlier in our work, we identified two compounds that have affinity for mPRs of different subtypes but do not interact with nPRs. Their actions have been demonstrated in various cells but have not been studied in vivo. In this work, the main aim was to study the action of one of these steroids (LS-01) in a classical test for pregnancy maintenance in ovariectomised female rats and for stimulation of the labour process to identify the role of mPRs. To analyse the main targets of mPRs selective ligand action in utero, we examined the expression of all five mPRs subtypes as well as nPRs and the membrane component of the progesterone receptor (PGRMC1) before, during and after pregnancy termination. From this study, we did not detect an effect of LS-01 on either pregnancy maintenance or labour induction in rats. However, the study of progesterone receptor expression profile and correlations of this profile with serum sex steroid concentrations suggests a different role of membrane receptor subtypes: progesterone acting through mPRγ and nPRs may promote pregnancy maintenance, while acting through mPRβ may promote labour initiation. To identify the functions of different subtypes of mPRs in reproduction and the fine regulation of this process, the search for ligands selective for each membrane receptor is necessary.

The aim of this study was to compare the effects of intragastric administration of saturated and unsaturated fats of vegetable and animal origin for 37 days on behavioral characteristics in rats with a systemic inflammatory response (SVR). In parallel, the severity of ischemic-reperfusion injury (IRF) of the myocardium was evaluated using the global ischemia-reperfusion model of an isolated heart, as well as the mass fraction of fat in the brain and the levels of a number of cytokines and biologically active substances in blood plasma. The effects of a fat-carbohydrate diet of different composition on experimental endpoints were compared with the effect of probiotic therapy. The animals were assigned to one of 7 groups (n = 8 in each group): 1) control; 2) chemically induced colitis on the 30th day of the experiment and three-day administration of antimicrobial drugs; 3) probiotic correction: during the last 8 days of the experiment, a mixture of probiotic strains of Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis was administered; 4) sunflower oil and sucrose; 5) ghee and sucrose; 6) dehydrated margarine and sucrose; 7) ghee + sucrose. The systemic inflammatory response that occurs in chemically induced colitis in combination with the transient use of antimicrobial drugs was characterized by an increase in the number of white blood cells and an increase in the level of proinflammatory cytokines in the blood, as well as a decrease in the mass fraction of fat in the brain. These changes reduced the resistance of the myocardium to ischemic reperfusion injury, but the preventive administration of various fat-carbohydrate compositions had no effect on this process. On the other hand, the systemic inflammatory response was accompanied by significant impairments of conditioned reflex activity, exploratory behavior, and coordination and motor function, whereas probiotic therapy and a fat-carbohydrate diet of different composition partially correct these impairments. The most pronounced effect on the selected experimental endpoints was exerted by the fat-carbohydrate diet, in which the fat component was represented by hydrogenated vegetable fat.

The objective is to analyze the amplitude-spectral indicators of electromyograms and their relationships with the performance of subjects during sensorimotor training in different social conditions of activity in dyads. The study was conducted on 256 subjects. As a model of activity, the sensorimotor training “Columns” of the software and hardware complex “BOS-Kinesis” (LTD “Neurotech”, Taganrog) was used with biological feedback from electromyographic signals from the radial flexor of the wrist (lat. flexor carpi radialis) of the leading hand of the subjects performing the task in 3 social contexts: individual, competitive and cooperative. As a result of the study of EMG characteristics of the sensorimotor activity of subjects in different social conditions, the following gender differences were revealed: at the individual stage, women have higher frequency characteristics of EMG, and men have higher amplitude and power of the EMG spectrum at the stages of competition and cooperation. The dynamics of EMG characteristics in women, unlike men, is associated with changes in social activity conditions. The variability of the frequency characteristics of the EMG spectrum increased in both men and women under joint activity conditions. Opposite directions of changes in the variability of the integral amplitude and total power of the EMG spectrum in joint activity contexts compared to individual ones were found: an increase in these indicators in men, but a decrease in women. In the female sample, the training performance correlated positively with the average EMG frequency values in all activity contexts, and negatively with the amplitude and power of the EMG spectrum during cooperation. The performance of men and women in all sensorimotor activity conditions correlated negatively with the variability of EMG characteristics. The results of the study contribute to the understanding of the features of the implementation of voluntary human movements when performing sensorimotor tasks in various conditions of social interactions. The obtained data can form the basis for identifying prognostic criteria for the effectiveness of joint sensorimotor activity to create methods for selecting successful teams and optimizing production processes.

The use of hyperbaric oxygen (HBO₂) in medicine and in underwater diving is associated with the risk of its toxic (convulsant) effect on the central nervous system, the pathophysiological mechanisms of which have not been sufficiently studied. A common hypothesis about the mechanism of HBO₂-induced convulsions is the idea that extreme hyperoxia suppresses GABAergic function with subsequent increase in CNS excitation, leading to convulsions. The deficit of GABAergic function in HBO₂ is due to a decrease in the synthesis of the mediator, while the involvement of other components of inhibitory neurotransmission, in particular, GABA receptors, remains unclear. The aim of this work was to study the involvement of GABA receptors in the development of hyperbaric oxygen convulsions. In the course of the work, motor convulsions in HBO₂ were assessed in rats that were injected with GABA receptor agonists: muscimol or baclofen into the lateral ventricle of the brain before hyperoxic exposure. The affinity of GABA receptors to these drugs was also assessed against the background of an increased level of cerebral GABA caused by intraventricular administration of nipecotic acid. New data from the studies are: (a) activation of GABA-A receptors with muscimol delayed the onset of seizures in HBO₂, (b) the GABA-B receptor agonist baclofen weakened the development of hyperbaric oxygen seizures, but its anticonvulsant effect was reliably lower than that of muscimol, (c) the anticonvulsant efficacy of muscimol and baclofen was preserved with an increase in extracellular GABA caused by inhibition of GABA transporters with nipecotic acid. The affinity of GABA-A and GABA-B receptors to the inhibitory neurotransmitter did not change under conditions of hyperbaric hyperoxia.

The spinal cord may be divided into segments. The neural networks of different segment groups control, in particular, locomotion and visceral functions. Spinal cord segments serve as critical topographic landmarks for both experimental and therapeutic interventions. However, accurate identification of segment positions in vivo, particularly through automated methods, remains challenging: in mammals, some spinal cord segments are displaced rostrally (ascend) relative to their corresponding vertebrae, and the extent of this displacement varies even within a single species. One solution to this problem may be the use of reference images of slices of segments taken, for example, from histological atlases of the spinal cord. In this paper, we investigate various methods for analyzing the similarity of gray matter contours in transverse slices of the mammalian spinal cord, which allow us to determine whether a slice belongs to a certain segment. We consider the methods for analyzing slices obtained from one animal (based on the Jaccard coefficient, the metric of distances between contours, correlation analysis of R-φ curves, or Hu invariant moments), as well as the methods for comparing images of spinal cord segments with reference ones (correlation analysis of R-φ curves, Hu invariant moments). The results obtained allow us to assume that the method of determining segments by comparing tomographic or histological images of spinal cord transverse slices at different levels with a certain database containing a set of reference images of slices of specific segments, based on Hu invariant moments, is the most effective of those considered.