Vol 109, No 9 (2023)

Nowadays there is a number of neuropsychiatric diseases that are considered to be associated with early life stress. Various models are used on laboratory rodents to elucidate the mechanisms of the pathogenesis of psychopathologies that cannot be studied in humans. For successful translation of data, it is necessary to compare the processes of neuroontogenesis at the moment of exposure and subsequent periods. There are many comparative studies concerning the development of neurons and neuronal networks, as well as changes in the hypothalamic-pituitary-adrenal axis. In recent years, it has been reliably shown that glial cells are an important participant in both brain development and its response to stress. The opinion that it is microglia and astrocytes that represent the most promising targets for therapeutic intervention in stress-related diseases is supported. However, there are still no comparative analytical studies covering both stress-realizing systems and neuronal and glial markers of development. This review fills this gap. Here we provide a new perspective for considering the problems of modeling childhood stress and translating the data obtained. The presented analysis, on the one hand, supplements the existing understanding of the correspondence between the stages of brain development in laboratory rodents and humans, and, on the other hand, marks points of growth and raises new questions for researchers of stress in early ontogenesis.

Parkinson’s disease (PD) is a progressive age-related neurodegenerative pathology of the central nervous system, characterized by a selective loss of dopaminergic neurons of the nigrostriatal pathway and by the presence of specific inclusions (Lewy bodies) in dopamine neurons. To study the mechanisms of this pathology and to search for possible ways to correct it, genetic models of PD in mice have been created. Transgenic mice of the B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J strain (referred as B6.Cg-Tg further in the text) represent a model of PD, have the A53T mutation in the human alpha-synuclein gene. The aim of this work was to study the locomotor activity and the level of anxiety, as well as the density of neurons in the brain of male B6.Cg-Tg mice at the age of six months. Wild type C57BL/6J mice of the same sex and age were used as controls. The results of the current study demonstrate that B6.Cg-Tg mice are characterized by the high locomotor activity and the low anxiety. Besides, a selective decrease in the density of neurons in the subventricular zone, the substantia nigra, as well as the CA1, CA3, CA4 zones and the granular layer of the dentate gyrus of the hippocampus was observed in these mice. Thus, mice of the B6.Cg-Tg strain at the age of six months only partially correspond to the main pathophysiological signs of PD. Decrease in the density of neurons in the substantia nigra, as well as in the CA1 and CA3 zones of the hippocampus of B6.Cg-Tg mice resemble similar changes in PD. However, these mice demonstrated neither bradykinesia nor high level of anxiety.

The article is focused on the study of the electrical remodeling of the “sports heart” using multichannel ECG mapping to make a more detailed and informative analysis of the excitation of the myocardium remodeled by sport activity. The study of the heart electrical activity was carried out from 64 unipolar electrodes on the thorax surface synchronously with standard limb leads in highly trained cross-country skiers (n = 15) and young non-trained men (n = 19) at rest. The amplitude-temporal and spatiotemporal characteristics of the electric field of the heart were measured. By the typical distribution of areas of the negative and positive cardiac potentials the durations of depolarization and its individual phases were estimated. ECG_II was used to determine the duration of the R-R, PQ (PR), QRS, QT, QTc intervals; in the unipolar lead V₅ the R-wave peak time (RWPT_V5) was measured. In athletes, the duration of PQ_II, QT_II, QTc_II, RWPT_V5 intervals were statistically significantly longer than in non-trained men. Analysis of the electrical field of the heart showed a difference in the ratio of the phases of ventricular depolarization in athletes and non-trained individuals at rest. The onset of ventricular depolarization and the first inversion of cardiac potential in athletes were significantly earlier than in non-trained people, while the completion and total duration of the period of ventricular depolarization did not differ. In skiers, the duration of the first inversion was significantly longer than in non-trained individuals; a tendency to shortening of the second period of stable location of potentials on the thorax surface was also shown. The use of surface ECG mapping made it possible to reveal differences in the spatiotemporal organization of heart ventricular depolarization between cross-country skiers and non-trained men at rest. The results of the study may be useful in the analysis of the electrical remodeling of the heart in athletes training the physical quality of endurance.

Vasopressin (VP) is one of the main factors affecting intraglomerular hemodynamics, filtration pressure and the state of mesangial cells and contributing to the progression of proteinuria. The aim of this work was to study the effect of neurohypophyseal hormones (VP and oxytocin) on urinary protein excretion. Experiments were performed on Wistar rats, healthy and with microalbuminuria caused by minimal damage to the glomerular filter. Microalbuminuria was modeled by administration of D-nitroarginine methyl ester (D-NAME, 50 mg/kg, intraperitoneally). VP (0.05 and 1.5 nmol/kg) and oxytocin (0.15 nmol/kg) were administered to rats intramuscularly, V₂-antagonist (15 nmol/kg) and V_1a-antagonist (20 nmol/kg) intraperitoneally. To reduce the level of endogenous VP, animals were given water to drink (10 ml/kg), urine was collected for 2 h, and the levels of total protein, albumin, β₂-microglobulin, and immunoglobulin G (IgG) were analyzed. In healthy rats, VP at a dose of 0.05 nmol/kg and oxytocin did not affect albumin excretion, but VP at a dose of 1.5 nmol/kg provoked microalbuminuria. In a model of impaired properties of the glomerular filter caused by the D-NAME administration, VP at a dose of 0.05 nmol/kg and oxytocin led to the normalization of albumin excretion, and VP at a dose of 1.5 nmol/kg caused pronounced proteinuria, albumin excretion increased by 100 times, IgG – by 10 times. Blockade of V₂ receptors aggravated protein loss caused by D-NAME and VP (1.5 nmol/kg), while blockade of V_1a receptors prevented it. Thus, at high concentrations in the blood, VP enhances protein filtration in the kidney. This effect is mediated by V_1a receptors and, depending on the barrier properties of the glomerular filter, leads to the development of microalbuminuria or severe proteinuria. Oxytocin and VP at a dose at which it predominantly activates V₂ receptors have an antiproteinuric effect. The revealed effects of neurohypophyseal hormones on albumin excretion open up new promising therapeutic targets for the correction of glomerular dysfunctions.

Serotonergic and nitrergic systems of the medial prefrontal cortex (mPFC) are involved in the control of fear generalization, but their local interaction during this function has been little studied. The aim of the work was to study the effect of blockade of endogenous nitrergic signals on serotonin release in the mPFC during the acquisition of a conditioned fear response (CFR – a fear model) and on the dynamics of its generalization. In male Sprague-Dawley rats using intracranial microdialysis in vivo and high-performance liquid chromatography with electrochemical detection, we found that the intra-mPFC infusion through the dialysis probe of the NO synthase inhibitor N-ω-nitro-L-arginine (NA, 0.5 mM) and selective neuronal NO synthase inhibitor N-ω-propyl-L-arginine (NPLA, 2mM) decreased the basal level of extracellular serotonin in the mPFC and reduced its rise, caused by the CFR acquisition (a paired presentation of a conditioned cue (CS+) and inescapable footshock). The intra-mPFC infusion of NA and NPLA increased animals’ freezing to a differential cue (CS–) not associated with footshock, during the first test, carried out 70 minutes after the CFR acquisition, but reduced it during repeated testing a day after the infusion, without changing freezing of the same animals to the potentially dangerous CS+. The data obtained indicate the involvement of endogenous NO in the activation of serotonin release in the mPFC, caused by the CFR acquisition. In addition, they show that the blockade of endogenous nitrergic signals of the mPFC, which enhances the initial generalization of the fear reaction, contributes to the extinction of the generalized fear, possibly due to inhibition of the serotonin release in the mPFC.