Žurnal èvolûcionnoj biohimii i fiziologii

The integrated stress response (ISR) is a mechanism of cellular response to various stress signals that is conserved in all eukaryotes, from yeast to humans. A central element of IOS is phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). This process is regulated by four kinases: PERK, GCN2, HRI and PKR, each of which is activated by different stress conditions. The ISR plays a critical role in maintaining cell homeostasis and survival under stress, but chronic activation can lead to cell dysfunction and programmed cell death. Recent studies indicate that IOS is actively involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis and traumatic brain injury. At the same time, the contribution of IRS to mental pathologies such as depression, schizophrenia, bipolar disorder, post-traumatic stress disorder and addiction remains poorly understood. This article reviews current data on the role of IRS in the pathogenesis of these disorders, and also discusses the possibilities of pharmacological modulation of IOS pathways in the pathological contexts.

The morphofunctional features of the bone marrow of the femur and humerus in long-tailed ground squirrels were studied in summer, fall, during torpor and during periods of short-term awakenings in winter (winter euthermia). Histological analysis showed an increase in the number and size of adipocytes in the bone marrow in animals in the torpor state, with partial replacement of myeloid tissue by adipose tissue. Despite the greater volume of bone marrow in the femur, significantly fewer nuclear cells were found in the bone marrow than in the humerus, but significantly more erythroid islets were found, especially during hibernation. In torpid ground squirrels there is a replacement of disc-shaped erythrocytes in the blood by atypical forms of erythrocytes (oval, macrocytes, and michenoid), the number of which decreases significantly during the winter euthermal period. The level of reticulocyte content increases in the hibernation period twofold compared to summer. The results obtained are discussed in the context of maintaining high blood oxygen levels during torpor and adaptation of erythropoiesis to conditions of prolonged hypothermia.

Bivalves as inhabitants of the littoral zone of the World Ocean are subjected to fluctuations in abiotic environmental factors. Sharp fluctuations in environmental parameters are accompanied by the development of a physiological stress reaction in the organism of mollusks, while changes in their functional state occur due to the release of neurotransmitters into the hemolymph. Catecholamines are key signaling molecules in the system of neuroendocrine regulation of bivalve mollusks and also are involved in the modulation of the immune response during physiological stress. Hemocytes, as the central effector of the cellular immunity of bivalve mollusks, have adrenoreceptors on the surface of the cell membrane, which suggests the presence of a functional relationship between external stress and the cellular immune response. In the present work, the effect of adrenaline at concentrations of 1 and 10 μM on phagocytosis, adhesion and aggregation capacity of hemocytes of the Mediterranean mussel Mytilus galloprovincialis (Lamarck, 1819) was investigated in vitro. The effect of adrenaline on the level of spontaneous production of reactive oxygen species and on changes in the mitochondrial membrane potential of hemocytes was also studied. It was shown that stimulation of mussel hemocytes with adrenaline at a concentration of 10 μM contributed to a reliable increase in the ability to phagocytosis. Adrenaline at a concentration of 1 μM significantly increased the ability of hemocytes to adhere to a solid substrate. Also, stimulation of cells with adrenaline at 10 μM for 30 minutes led to an increase in the membrane potential of hemocyte mitochondria. No reliable changes in the level of spontaneous production of active forms of oxygen in hemocytes under the influence of adrenaline were detected. The results of this work indicate that adrenaline has an immunomodulatory effect on mussel hemocytes and stimulates their aerobic metabolism.

Temporal lobe epilepsy is a common neurological disorder that in many cases is accompanied by drug resistance. The current approach to the treatment of patients with drug resistance includes surgical intervention, which does not guarantee full recovery. At present, new antiepileptic drugs that affect signaling cascades inherent in epileptogenesis are being developed. The development of such drugs requires knowledge of the basic mechanisms of epilepsy pathogenesis. The aim of the work was to investigate the dynamics of expression of proteins involved in the regulation of apoptosis, circadian rhythms and antioxidant response in the temporal cortex of the brain during prolonged kindling in the Krushinsky-Molodkina (KM) rat model with hereditary audiogenic epilepsy. The dynamics of expression of studied proteins – p53, CLOCK, Nrf2, p105 - was investigated in the temporal cortex (immunohistochemistry, Western blotting). It was found that p53 level was lower in KM control rats than in Wistar rats. In KM rats subjected to 21 days kindling, p53 content is increased compared to KM control. CLOCK level was downregulated in the KM control group compared to the negative control and elevated in the KM group after kindling 21 days relative to the KM group after 7 days kindling. No changes in Nrf2 and p105 production were detected. The data obtained suggest that the changes in the levels of the studied proteins in control KM rats compared to Wistar rats are genetically determined. Induced epileptogenesis (kindling) for 21 days leads to activation of p53-dependent apoptosis pathway and, possibly, to desynchronosis - change of circadian rhythms. The findings contribute to the study of temporal lobe epilepsy mechanisms and require further studies related to mitochondrial apoptosis and sleep-wake cycle shift in the pathogenesis of temporal lobe epilepsy.