Vol 109, No 2 (2023)

It is known that melatonin modulates the daily and seasonal rhythms of metabolism. However, the effect of long-term intake of exogenous melatonin on the parameters of lipid and carbohydrate metabolism in various diets is still unclear. In our work, we conducted the meta-analysis of 53 publications investigating the effect of melatonin monotherapy on lipid and carbohydrate metabolism in rats kept on a standard diet (44 publications), as well as diets with a high content of fructose (7 publications), fats (11 publications) and cholesterol (5 publications). According to the literature, high fructose diet caused a significant increase in the levels of triglycerides, glucose and insulin in rats. In rats fed high fat diet, an increase in triglycerides, total cholesterol (TC), insulin, and a decrease in high-density lipoprotein (HDL) was observed. In rats kept on high cholesterol diet an increase in the level of TC and a decrease in the concentration of HDL was observed. Melatonin therapy reduced triglyceride, TC, and insulin levels but did not alter glucose levels in rats fed diets rich in fructose and fats. On a cholesterol-rich diet, melatonin decreased TC levels and increased HDL and glucose levels, but did not change triglyceride concentrations. Our meta-analysis found no beneficial effect of increasing the dose of melatonin with fortified diets. With a standard diet, long-term melatonin therapy also reduced insulin levels, but had no effect on TC and increased glucose levels. The deterioration in carbohydrate metabolism was associated with higher doses of melatonin at the beginning of therapy, with intraperitoneal administration or with administration through a gastric tube, with administration in the light phase. In addition, high doses of melatonin have been associated with poor lipid metabolism in the standard diet. The effect of melatonin was directed towards minimizing changes in the lipid profile caused by diet, which confirms the homeostatic role of melatonin in lipid metabolism.

Alzheimer’s disease (AD) is an incurable neurodegenerative disease that is the main cause of dementia in the elderly. When looking for new treatments for AD, attention was drawn to the multifunctional Y-box-binding protein 1 (YB-1). Previously, we revealed a positive effect of intranasal administration of YB-1 on learning and spatial memory, along with a decrease in the content of cerebral β-amyloid and the intensity of plaque initiation, with an improvement in the survival of neurons in the cortex and hippocampus of male AD mice. However, AD affects women twice as often as men, so it is of great interest to study the effects of YB-1 on aging females. Estrogens and androgens are necessary for the maintenance of cognitive function during aging and, apparently, may prevent the development of AD. In this work, peripheral levels of estradiol (E2) and cytokines were studied after intranasal administration of YB-1 to aging female 5xFAD transgenic mice and control non-transgenic animals. In intact aging animals of both groups, a violation of the estrous cycle and a decrease in the level of E2 in blood plasma were revealed. Mice treated with YB-1 did not show a characteristic age-related decrease in plasma E2 levels. The introduction of YB-1 did not affect the peripheral level of cytokines. Thus, a novel, previously undescribed effect of YB-1 on plasma E2 levels in aging female mice is shown. These data indicate that YB-1 may be a promising compound in the prevention and treatment of neurodegenerative diseases. However, further experiments are needed to gain insight into the detailed mechanisms of YB-1 action.

In experiments on the sagittal hypothalamic slices of male Wistar rats, the effects of 15 nM insulin on the level of spike activity, parameters of spike information coding by the suprachiasmatic nucleus neurones, and functional state of afferent inputs to the neurones from the arcuate nucleus were studied. Application of insulin induced a decrease in the frequency of action potential generation and an increase in the entropy of interspike interval distribution in 33.3% of neurones recorded; in 12% of cells, the responses of opposite direction were found; in the remaining 54.7% neurones, spike activity did not change. The responses of the entropy of interspike interval distribution suggest the related changes in a degree of interspike interval irregularity induced by insulin. To characterise afferent inputs to the suprachiasmatic nucleus neurones from the arcuate nucleus, electrophysiological technique of the construction and analysis of the peristimulus time histogram (PSTH) was used. Statistically significant responses to the stimulation of the arcuate nucleus were recorded in 24 of 38 neurones of the suprachiasmatic nucleus. In 6 of the neurones, the responses were in the form of a short-latency (<20 ms) excitation, in 1 neurone in the form of a long-latency excitation, in 6 neurones in the form of a short-latency inhibition; in 11 neurones complex two- or three-phase responses in the form of different compositions of excitation and inhibition were observed. Application of 15 nM insulin induced a qualitative transformation of the responses (disappearing of the initial responses or emergence of new responses) in 5 neurones initially responded to stimulation, and in 1 neurone initially not responded to stimulation of the arcuate nucleus. Statistically significant changes in the latency or duration of the responses in the presence of insulin were not found. The results of the study suggest the ability of insulin to influence the activity level and the spike code of a respectively numerous population of neurones in the suprachiasmatic nucleus circadian oscillator as well as modulate the functional state of afferent inputs to the circadian oscillator from hypothalamic arcuate nucleus playing an important role in the control of appetite and metabolism.

Recently, more and more attention has been paid to the discussion of the trophic function of the nervous system and its participation in the launch of signaling cascades regulating cellular metabolism. The role of acetylcholine and Na⁺,K⁺-ATPase in the regulation of skeletal muscle growth in 10–12-day-old chicken embryos under conditions of organotypic tissue culture was evaluated. The maximum trophotropic effect of acetylcholine was shown in a concentration 10^–8 M. Inhibitory analysis proved the participation of the nicotinic acetylcholine receptor in this effect. Ouabain dose-dependent regulated the growth of skeletal muscle tissue explants. In concentrations comparable to endogenous ones, the glycoside stimulated the growth of experimental explants by 33% compared to the control value. The myotoxic properties of ouabain were found in the concentration range 10^–6–10^–4 M. Acetylcholine eliminated the myotoxic effect of the ouabain (10^–6 M) both directly acting on the Na⁺,K⁺-ATPase, and the receptor-mediated through the nicotinic acetylcholine receptor.

Absence epilepsy is a specific generalized non-convulsive form occurring almost exclusively in children and adolescents. It is traditionally thought that the resulting seizure is completely generalized in the cortex of both hemispheres, as seen in humans on surface electroencephalograms and magnetoencephalograms. However, most studies were performed on animals, mainly rats – genetic (WAG/Rij and GAERS lines) and pharmacological models, since signals not only from the cortex, but also from subcortical structures such as the thalamus must be measured, what cannot be done on humans, who have no medical indications for intracranial surgery. In animals, measurements of local field potentials were almost always made from one hemisphere in order to cover the maximum number of brain structures involved. At the same time, the degree of synchrony of seizure onsets and terminations in different hemispheres in animals was practically not studied, and the markup itself in the vast majority of cases was done on the basis of one channel from motor or somato-sensory cortex. This work aims to reveal differences and similarities in the course of spike-wave discharges (the main encephalographic marker of absence seizures) in the cortex of the two hemispheres in a known pharmacological model of rats exposed to pentylentetrazole. For discharge detection, a method of automatic discharge marking is proposed and its sensitivity and specificity are evaluated using records of nine animals. We used it to mark seizures in symmetrical cortical sites from both hemispheres separately. According to the results of the analysis of seizure duration it turned out that for five out of nine animals the distribution of discharges significantly differed between the hemispheres, and for the other four was equal. Consequently, in the rat model, spike-wave activity may be generalized both symmetrically and asymmetrically, which may be due to individual peculiarities or different discharge triggering scenarios.