Vol 59, No 5 (2023)

The article analyzes the literature data on the role of molecular olfactory receptors (OR) and cAMP in the formation of the topographic organization of the olfactory sensory system. Before its transmission to the brain, sensory information is already organized in the peripheral region according to the “one neuron–one receptor” principle, which also extends to the glomeruli in the olfactory bulb, which obey the “one glomerulus–one receptor” law. At present, an important role in the formation of the sensory map has been attributed to ORs, which plays a dual role in the organization of the olfactory system, since they are localized both in the olfactory cilia (OC) and in the membrane of the axon growth cone of the same olfactory sensory neuron (OSN), and determine the target for the axons of the OSN in the olfactory bulb (OB). However, there is strong evidence for the central role of the intracellular cAMP signaling system in sensory map development. Using the method of genetic mutation with the abolition of cAMP synthesis, it was revealed that the axons carrying this mutation never penetrate the glomerular layer, but remain in the layer of the olfactory nerve. At the same time, OSN axons target the OB but fail to form distinct and well-defined glomeruli, many of which become heterogeneous because they contain fibers belonging to OSNs expressing ORs for different odorants. Thus, cAMP synthesized in the tip of the RSN axon, under the action of signals from the OB, regulates the expression of molecules of its navigation to its target in the OB, and also forms intrabulbar chemical and electrical synapses, forming neuronal circuits. Numerous clinical and experimental data have led to the conclusion that the pathogenetic mechanisms of the development of some psychiatric diseases are associated with dysregulation of cAMP.

The effect of infection of Tetrabothrius minor (Cestoda: Tetrabothriidae) on the protease activity of the mucous membrane of the small intestine of the Northern Fulmar Fulmarus glacialis was studied. Aspects of changes in the activity of proteases and protease subclasses (metalloproteases, serine proteases and cysteine proteases) by infection of T. minor, and the ability of T. minor to inactivate proteases from the intestinal mucosa and commercial trypsin were evaluated. It has been established that in the localization of T. minor (proximal and medial sections of the small intestine) decreased protease activity due to a decrease in the activity of serine proteases and metalloproteases. The dependence of the decrease of protease activity in the mucous membrane of the small intestine of the host on the parameters of infection with cestodes was found – the higher the infection intensity of T. minor, the lower the activity of proteases, including metalloproteases and serine proteases. The ability of T. minor homogenates to inhibit the activity of proteases from the mucosa of Northern Fulmar and the activity of commercial trypsin of different concentrations was noted.

A number of systemic heart diseases leading to the development of heart failure (aortic stenosis, hypertension, diabetic cardiomyopathy, reperfusion injury etc.) are accompanied by a pronounced reorganization of the T-system of cardiomyocytes, both in humans and animals. However, structural-functional changes within this membrane compartment of cardiomyocytes following ischemia-reperfusion (IR) have not been thoroughly studied. The aim of the work was to study the remodeling of the T-system in the subepicardial cardiomyocytes of the left ventricle of the rat heart after IR injury using confocal microscopy and extracellular recording methods. The study was carried out after 24 hours, two weeks, and four weeks following IR. A remodeling of action potentials, recorded extracellularly in the cardiomyocyte membrane patches devoid of t-tubule entrances (type 1 eAP), was observed. Starting from 24 hours up to 4 weeks after IR, there was an increase in the duration of their decline time (T₉₀) and the formation of eAP after-hyperpolarization phase, reaching maximum values by the fourth week after IR. A decrease in the second peak’s amplitude of eAPs, measured from cardiomyocyte surface locations with t-tubule openings, was also noticed four weeks after IR. In this investigation, no observable changes in the structural organization of the T-system were found. These data suggest that functional modifications of the epicardial cardiomyocyte T-system after IR injury may precede its structural modifications.

Stress effects on pregnant female disrupt the behavior and cognitive abilities of their offspring not only of the first, but also of the subsequent generations. A similar transgenerational effect on the offspring phenotype can be exerted by various stress factors that affect fathers before conception. The purpose of the study was to reveal the transgenerational effect of stress in female rats from 15–19 days of pregnancy on memory and expression of the insulin-like growth factor 2 (Igf2) gene in the brain of male and female offspring, as well as the effect of additional stress in the stress-restress paradigm in prenatally stressed male rats before conception on the memory and expression in the brain Igf2 of their offspring of both sexes. We have shown that prenatally stressed males and their next-generation male offspring show improved memory in the passive avoidance test, increased Igf2 expression in the hippocampus and cortex. Females, descendants of prenatally stressed males, on the contrary, showed a decrease in the duration of memory retention, Igf2 expression in the hippocampus and cortex. Additional stressing of prenatally stressed males before mating with intact females worsened memory and the duration of its retention, reduced Igf2 expression in the brain of the offspring of both sexes. We concluded that the transgenerational effects of prenatal stress on memory and Igf2 expression in the brain depend on the sex of the offspring, and prenatal stress itself in males contributes to memory impairment and a decrease in Igf2 expression in the offspring brain if such males were additionally stressed before mating.

Temporal lobe epilepsy is characterised by the development of associated neurological and psychiatric disorders. One of the possible causes is obviously a disturbance in the balance of the excitatory and inhibitory neurotransmitter systems of the hippocampus. Chronic abnormalities in the molecular mechanisms of regulation of hippocampal glutamatergic system activity in temporal lobe epilepsy are currently poorly understood. In the present study, we used Krushinsky–Molodkina (KM) rats subjected to repeated audiogenic seizures to simulate temporal lobe epilepsy. Molecular mechanisms of regulation of glutamate production by hippocampal neurons were analysed one week after the end of short-term (14 seizures) and long-term (21 seizures) kindling. In the hippocampus of КM rats, kindling results in activation of ERK1/2 kinases as well as activation of the transcription factor CREB and increased expression of the transcription factor Fra1, glutaminase and the vesicular glutamate transporters VGLUT1 and 2, that is proteins responsible for glutamate production. These data indicate increased activity of glutamatergic hippocampal neurons persisting for a week at rest after the completion of the last audiogenic stimulation. Enhanced expression of mGluR1 glutamate receptors, whose activation is known to result in Ca2+ release and increased excitotoxicity, is also shown. Long-term enhancement of glutamatergic transmission induced by repeated epileptiform seizures is not only responsible for further epileptogenesis, but may also underlie the development of neurodegenerative complications.