卷 40, 编号 1 (2023)

The review summarizes the results of recent studies on the mechanisms mediating the crossing by small extracellular vesicles through blood-brain barrier (BBB). The kinds of vesicular transport through the BBB, including receptor-mediated and adsorptive-mediated transcytosis, are considered. The possibilities of optimizing the penetration of vesicles into the parenchyma of the brain through the BBB are shown.

It is assumed that schizophrenia may consist of extremely heterogeneous group of phenotypes with different biological and neurochemical pathological mechanisms. At the same time, much attention is paid to the potential role of the immune system in the development of schizophrenia and, in particular, the participation of various cytokines in these processes. Interleukin-6 (IL-6) is one of the key regulators of inflammatory processes. A number of studies have previously reported changes in its levels in patients with schizophrenia. However, data on the specificity of these changes in the literature are much less well-documented and sometimes even contradictory. The dichotomous functioning of IL-6 may play a key role in the regulation of both pro- and anti-inflammatory processes. In this regard, the role of this cytokine in the etiopathogenesis of schizophrenia may depend on the phase of the disease and the context of the inflammatory process. The aim of this review was to analyze in detail the role of IL-6 in the mechanisms of schizophrenia and its potential impact on the course, diagnosis and therapy of this disease.

A possible mechanism for odors processing in a neural network that includes the olfactory bulb, the piriform cortex, the olfactory tubercle, which is the part of the ventral striatum, the ventral pallidum, the mediodorsal thalamic nucleus, and the orbitofrontal cortex, has been proposed. According to this mechanism, dopamine released by midbrain neurons in response to odor and reinforcement, as well as adenosine receptor antagonists, modulate in a certain way the efficacy of excitatory synaptic inputs to spiny cells of the olfactory tubercle projecting into the ventral pallidum. As a result, the neurons of the olfactory bulb are disinhibited by the ventral pallidum and contrasted odor representations are formed on them, as well as on their target cells in the piriform cortex. Simultaneously, there is a disinhibition of neurons of the mediodorsal nucleus and their target cells in the orbitofrontal cortex, which excites the neurons of the piriform cortex. This promotes the induction of LTP at the inputs from the olfactory bulb to the piriform cortex and the memorization of odor representations. For the first time it is pointed out that the mechanism for odor processing is similar to those we earlier proposed for processing of auditory and visual information in topographically organized cortico-basal ganglia-thalamocortical loops, which include the primary and higher areas of the auditory and visual cortex, as well as the prefrontal cortex. It is proposed that mechanism for olfactory processing is similar in vertebrates at different stages of evolution, including lampreys, due to the similarity of the functional organization of the basal ganglia and their interactions with other structures. It follows from the proposed mechanism that in cases when dopamine drugs are not effective in restoring the odor perception, it is desirable to use adenosine A2A receptor antagonists. Supporting this prediction is evidence of improved sense of smell in patients with COVID-19 when treated with A2A receptor antagonists.

Alzheimer’s-like disease was simulated in female adult Wistar CRL(WI) WUBR rats by 6-week intragastric administration of aluminium chloride at a dose of 200 mg/kg body mass. In the presence of developed oxidative stress (OS), we found a decrease in the activities of tricarboxylic acid cycle (TCA cycle) enzymes and an increase in the activities of pentose phosphate pathway (PPP) dehydrogenases as well as a reduction of SH-and SS-groups in proteins (P) along with the increased SH/SS ratio and glutathionylation with simultaneous decreases of glutathione (GSH) and the GSH/GSSG ratio and its redox potential in the brain hemispheres. The glutathione system enzymes were changed multidirectionally, with glutathione reductase remaining stable. Decreased activities of GSH biosynthesis enzymes and cysteine content were noticed. The intragastric administration of the CoA biosynthesis modulators D-panthenol (PL), D-pantethine or D-homopantothenate (HPA) at a dose of 200 mg/kg since the 5th week of the experiment caused either reduction or leveling of OS manifestations in blood plasma, an increase in acetyl cholinesterase, normalization of the activities of TCA cycle and PPP enzymes, P-SH level (not the SH/SS ratio) and a considerable reduction of S-glutathionylation as well as increases in GSH level, the GSH/GSSG ratio and redox potential in the hemispheres. The effect of CoA system modulators was manifested in activation of glutathione transferase, a decrease of glutathione peroxidase and less evident activation of GSH biosynthesis enzymes (PL) although they contributed to the elevation of cysteine content due to the reduced protein S-cysteinylation. The levels and the ratio of CoA/acetyl-CoA (except for PL) were not changed by toxicosis and the OS modulators. The feasibility of non-conenzyme effects was confirmed by the administration of HPA. The phenomenon of redox activity of the CoA biosynthesis modulators with clearly directional effects on the glutathione system and the TCA cycle and PPP enzymes during alleviation of OS and aluminium neurotoxicosis is discussed.

The results demonstrate and confirm the significant role of monoamine imbalance in the ictogenesis of Krushinsky–Molodkina rats with genetically determined audiogenic epilepsy and in the development of audiogenic kindling (AuK) in them. The experiments were carried out on rats of the Krushinsky–Molodkina (KM) line without sound stimulation (KM-background) and after the development of AuK (KM-AuK). The control group was rats of line “0”, in which convulsions in response to sound were completely absent. AuK was generated using 20-fold sound stimulation (120 dB). Neurochemical analysis was performed by HPLC/ED in the frontal cortex, hippocampus, hypothalamus, nucleus accumbens, and brainstem. It has been established that AuK in KM rats leads to the appearance of myoclonic and attenuation of stem convulsions, which is accompanied by a change in the functional activity of the noradrenergic and serotonergic systems of the brain. KM rats exhibiting tonic convulsions in the “background” have a low content of norepinephrine in the hippocampus and hypothalamus, and when audiogenic myoclonic convulsions develop, norepinephrine deficiency is observed in the frontal cortex. After the formation of AuK, the excessively intense serotonin metabolism revealed in KM slows down in the hippocampus, nucleus accumbens, and, especially, in the brainstem, and the serotonin deficiency in the striatum also disappears. The peculiarities of norepinephrine metabolism in KM rats before and after AuK emphasize the important role of the cortex in the development of myoclonic convulsions, and of the hippocampus and hypothalamus in the implementation of stem convulsions. Excessive functional activity of the serotonergic system, revealed in KM “background” rats, slows down in a number of brain structures during the production of AuK.

One of the pathophysiological mechanisms of the development of some mental diseases, including depressive disorders, is a decrease in the expression of brain-derived neurotrophic factor (BDNF), mainly in the limbic region and prefrontal cortex of the brain. Immunochemical screening of BDNF in biological fluids showed that the levels of this protein can be considered as a marker of predisposition to depression and a prognostic marker of the effectiveness of therapy. The use of modern technologies for the production of recombinant proteins makes it possible to develop highly standardized ELISA systems for the determination of this antigen in biological fluids. This paper describes a method for creating a test system for quantitative ELISA of brain-derived neurotrophic factor on the basis of recombinant protein BDNF and antibodies obtained as a result of immunization with recombinant BDNF.

The role of chemokines involved in the processes of neuroinflammation is not well understood in schizophrenia, especially in patients with the first episode of the disease. The aim of the study: to study the content of pro-inflammatory chemokines in the blood of patients with the first episode of paranoid schizophrenia. We examined 18 patients with a diagnosis of F20.09, the control group – 35 people. Determination of the content of 13 chemokines in blood serum was carried out by flow fluorometry. Blood sampling was carried out before the start of therapy. In patients with the first episode of schizophrenia before the appointment of therapy, an increase in the blood level of CCL4 (MIP-1β) by 1.1 times, CXCL9 (MIG) – by 1.4 times, CCL11 (Eotaxin), CXCL5 (ENA-78), CXCL10 (IP-10) – 1.5 times, CXCL1 (GRO-α) – 1.6 times, СCL20 (MIP-3α) – 2.1 times, CXCL8 (IL-8) – 21.0 times. The results obtained indicate the importance of neuroimmune inflammation in the manifestation of schizophrenia with the involvement of chemokines in this process.