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Volume 42, Nº 2 (2025)
- Ano: 2025
- Artigos: 12
- URL: https://journals.rcsi.science/1027-8133/issue/view/24342
Articles
In Memory of Professor Nina Konstantinovna Popova: Memories of Colleagues and Students
Neurochemical Journal. 2025;42(2):183-196
183-196
SCIENCE AND LIFE, AND LIFE IS SCIENCE. IN MEMORY OF NINA KONSTANTINOVNA POPOVA
Neurochemical Journal. 2025;42(2):197-199
197-199
Dual Functions of Mature and Immature Brain Neurotrophins in Regulating Neuroplasticity and Their Modification by Glucocorticoids
Resumo
Neurotrophic factors play an essential role in the ontogeny of the newborn brain, determining the vectors for the development of the regulatory systems of the organism. Changes in the expression of neurotrophic factors under conditions of elevated glucocorticoid levels or stress, according to the results of clinical observations and animal studies, are associated with the etiology of psychoenotional disorders and neurodegenerative pathologies. The hippocampus is a link for the manifestation of the modifying effects of glucocorticoids and stress effects on the processes of neuroplasticity and behavioral regulation in the brain. The manifestation of psychopathological and neurodegenerative changes is accompanied by modulation of the expression of key neurotrophic factors in the hippocampus, including after glucocorticoid induction, while the balance of expression of proforms and mature proteins of neurotrophins is extremely important. Thus, the main problem of this mini-review is to highlight the modification of expression of brain-derived neurotrophic factors, mature and immature forms of BDNF, NGF and NT3 mainly in the neonatal CNS, in particular in the hippocampus, under the influence of glucocorticoids, neuropathologies or effects of stress various etiologies based on literature and our own data. It was established that it is proBDNF, and not proNT3 and proNGF, that has its own expression pattern in the hippocampus of neonatal rats, under dexamethasone induction, different from its mature form, and the manifestation of the proapoptotic effect of this proneurotrophin is accompanied by an increase in the proBDNF/BDNF ratio and an increase in the number of cells with detectable active caspase-3.
Neurochemical Journal. 2025;42(2):200–209
200–209
BIPOLAR AFFECTIVE DISORDER AND CLINICAL DEPRESSION: COMPARATIVE ANALYSIS OF THE SEROTONERGIC SYSTEM ROLE IN PATHOGENESIS AND CORRECTION
Resumo
The search for potential biomarkers to facilitate differential diagnosis and improve its accuracy is one of the primary tasks of modern psychiatry. In actual clinical practice, distinguishing bipolar affective disorder (BAD) from unipolar (clinical) depression is often difficult. There are a large number of animal models that recreate depression-like behavior, while the study of the BAD pathogenesis mechanisms is complicated by the almost complete absence of experimental models that adequately imitate both the manic and depressive phases of this disorder. Today, there is no doubt about the involvement of the monoamine serotonin (5-HT) system in the pathophysiology of both unipolar and bipolar depression. The similarity of the clinical picture of the depressive episode of BAD and unipolar depression suggests common mechanisms, while the presence of the manic episode of BAD, on the contrary, implies opposite changes, including in the level of central 5-HT signal transduction. However, given the sufficient study of the 5-HT system role in the pathogenesis of clinical depression and its successful correction by selective serotonin reuptake inhibitors (SSRIs), the significance of its involvement in the processes of manifestation of BAD, as well as in the mechanisms of «phase switches», remains a debatable issue. The aim of this review was to compare the pathogenesis of uni- and bipolar depression (including depressive and manic episodes) and the diversity of their experimental models, as well as to analyze the contribution of key elements of the 5-HT system (5-HT, its precursors and main metabolites, 5-HT1A autoreceptor, 5-HTT transporter) into the pathophysiology of disorders.
Neurochemical Journal. 2025;42(2):210-225
210-225
AUDIOGENIC SEIZURE FITS AND POSTICTAL CATALEPSY IN RATS OF KRUSHINSKY–MOLODKINA STRAIN
Resumo
The main peculiarities are described of rodent audiogenic epilepsy (seizure fits in response to loud sound), which is the complicated trait connected to brain neurochemistry, displaying peculiarities in a range of brain metabolites as well as to the deviations of muscle tone regulation. Selected for audiogenic epilepsy rat strain Krushinsky–Molodkina is the valuable genetic model of human seizure states. The pattern of neurochemical deviations in this strain is similar to those in other rodent strains with audiogenic epilepsy, which permit to suggest the non-random nature of these phenomena. The post-ictal catalepsy and cataleptic states of other groups are discussed in connection with audiogenic seizure fits. Brain anomalies in these animals emerge, presumably, during early ontogeny.
Neurochemical Journal. 2025;42(2):226-233
226-233
Gene Expression Levels of DNA-Methyltransferases and Histone Deacetylases After Neonatal Dexamethasone Administration and Chronic Unpredictable Stress in Adult Rat Brainstem
Resumo
Epigenetic modifications of DNA and chromatin structure are involved in the long-term consequences of adverse early ontogenesis events. Increased glucocorticoid levels due to stress or hormonal therapy in early life provoke the development of autism spectrum disorders, attention deficit syndrome, and increase with age the susceptibility to depressive-anxiety disorders in adult animals regulated by the noradrenergic and serotonergic systems, the perikarya of which are localized in the brainstem. The aim of the study was to determine the expression levels of DNA methyltransferase (Dnmt1, Dnmt3a, Dnmt3b) and histone deacetylase (Hdac1, Hdac2) genes in the brainstem of adult two-month-old rats after a single administration of the glucocorticoid receptor agonist dexamethasone (0.2 mg/kg) on the 3rd day of life, as well as the effects of chronic unpredictable stress in the late adolescent period of development (from 45 to 60 days of life). It was established that neonatal administration of a glucocorticoid receptor agonist in the sensitive period of early postnatal ontogenesis causes long-term changes in the expression of DNA methyltransferase and histone deacetylase genes - increases the mRNA levels of the Dnmt3a, Dnmt3b and Hdca1 genes in the brainstem of adult animals. The induction of expression of the main regulators of DNA methylation and chromatin conformation, which was established for the first time, is preserved for the Dnmt3b and Hdca1 genes under the influence of chronic unpredictable stress. The revealed patterns can provide a decrease in the expression of epigenetically regulated transcripts in the brainstem, which is important for understanding the mechanism of long-term consequences of unfavorable conditions of early development.
Neurochemical Journal. 2025;42(2):234–243
234–243
Evaluation of Mitochondrial Activity in Neural iPSC Derivatives Obtained from a Parkinson’s Disease Patient with Genetic Variant C.1492T>G of GLUD2
Resumo
Parkinson’s disease (PD) is a progressive neurological disorder that can be inherited through pathogenic variants of certain genes. While variants of some genes have been linked to PD, the specific role of variant c.1492T>G in the GLUD2 gene in PD development remains unclear. The GLUD2 gene is located on the q arm of the X chromosome and is a pseudogene for GLUD1, which encodes for glutamate dehydrogenase type 1. Both GLUD2 and GLUD1 are involved in the regulation of glutamate levels in the brain, and their dysfunction has been linked to PD. However, more research is needed to fully understand the role of this particular variant in PD pathogenesis. Previously, induced pluripotent stem cells (iPSCs) from a patient with PD [PD40], were generated in the laboratory of developmental epigenetics at the Institute of Cytology and Genetics SB RAS. The patient is a 55-year-old man with a hemizygous genotype, carrying a pathogenic missense mutation (c.1492T>G, p.S498A, rs9697983) in the GLUD2 gene that leads to increased activity of the hGDH2 mitochondrial enzyme. In this study in patient-specific cells (iPSC-derived astrocytes and dopaminergic neurons), we have shown for the first time the proposed contribution of this variant to mitochondrial function in PD.
Neurochemical Journal. 2025;42(2):244-254
244-254
POSSIBLE MECHANISM OF REPETITIVE STEREOTYPIC MOVEMENT PATTERNS IN AUTISM SPECTRUM DISORDERS (A ROLE OF NEUROMODULATORS)
Resumo
A possible mechanism for repetitive stereotypic movement patterns (SMPs) in autism spectrum disorders (RAS) has been proposed. We used known data on the abnormal functioning of the neural network, including the neocortex, basal ganglia, thalamus, hippocampus and cerebellum. Taking into account the possible mechanism of functioning of this network that we proposed earlier, an analysis was carried out of the influence on its functioning of changes in the concentration of dopamine, adenosine, cannabinoids and corticoids that are characteristic of ASD. From the proposed mechanism it follows that the weakening of motor activity, one of the manifestations of which is SMPs, can be facilitated by antagonists of Gs and Gq/11 protein coupled receptors on striatoniqral cells and agonists of receptors of this type on striatopallidal cells, as well as antagonists of Gi/0 protein coupled receptors on striatopallidal cells and their agonists on striatoniqral cells. Taking into account the known data on the location of receptors on the striatal spiny cells, it follows from this mechanism that the most effective for weakening SMPs may be agonists of adenosine A2A and cannabinoid CB1 receptors, as well as antagonists of dopamine D2, histamine H3 and glucocorticoid receptors (or an effect that reduces cortisol level). When systemic using, these substances can weaken SMPs, both due to inhibition of thalamic neurons via the basal ganglia, and due to an increase in the activity of the subthalamic nucleus neurons and pyramidal neurons in the CA1 hippocampal area, the influence of which on the neocortex and amygdala prevents the shift from “cognitive” to “habitual” control of movements, which depends on the dorsal striatum. This mechanism allows to explain the strengthening and weakening of SMPs under the influence of stress and cannabinoids, respectively. The known results of clinical and experimental studies of SMPs provide evidence in favor of the proposed mechanism, which differs from those known from the literature. It may be useful in the development of new drugs for the treatment of SMPs in RAS.
Neurochemical Journal. 2025;42(2):255-270
255-270
Molecular and Neurochemical-Level Gears of CNS Response to Combined Impact of Modeled Spaceflight Factors in Rodents
Resumo
The combined model of the effects of deep space flight factors, developed at the IBMP RAS, includes ground-based modeling of the chronic synchronous effects of hypogravity and gamma radiation, supplemented by heavy ion irradiation, a factor characteristic of interplanetary flights. At the behavioral level, the result of such influences is a spectrum of disorders in the emotional sphere while maintaining cognitive abilities. Neurochemical studies in rats show multidirectional changes in the metabolism of key neurotransmitters, primarily dopamine and serotonin, in the ancient brain and prefrontal cortex. At the molecular level, there are changes in the expression of genes encoding the corresponding receptors. A malfunction of the dopaminergic system apparently causes emotional and behavioral disorders. Folic acid, a precursor of dopamine, corrects these changes and, thus, opens up the possibility for further search for means of prevention and treatment of the emerging pathology.
Neurochemical Journal. 2025;42(2):271–279
271–279
Neurochemical Markers of Efficacy of Selective Serotonin Reuptake Inhibitors and Resveratrol in Correcting Anxiety Disorders of Stressful Nature
Resumo
Anxiety-phobic disorders are behavioral complications of chronic stress. Unfortunately, there is still no effective pharmacological correction of them. The aim of the study was to assess the prospect of the combined use of resveratrol and selective serotonin reuptake inhibitors for the correction of anxiety-phobic disorders caused by chronic predatory stress. To reproduce anxiety-phobic disorders, a model of predatory stress was used, carried out by contact of rats with the smell of a fox. The anxiety level was determined in the elevated cruciform maze test. In the cerebral cortex, the content of serotonin, MAO-A activity and the intensity of lipid peroxidation (POL) were determined. It was found that chronic predatory stress was accompanied by an increase in anxiety, manifested in a decrease in the time spent in the open arms of the cruciform labyrinth and increased freezing. At the same time, serotonin levels and MAO-A activity increased in the brain, and the intensity of lipid peroxidation increased. Fluoxetine and citalopram alone could not effectively correct anxiety-phobic disorders. Resveratrol alone and together with fluoxetine and citalopram could both weaken and enhance anxiety-phobic disorders. The effects of resveratrol were dose-dependent. A decrease in stress anxiety as a result of pharmacological correction was accompanied by a restoration of serotonin levels to control values, a decrease in MAO-A activity and the intensity of POL in the brain. Resveratrol, both independently and in the presence of selective serotonin reuptake inhibitors, can effectively correct anxiety-phobic disorders in some cases and potentiate in others depending on the dose.
Neurochemical Journal. 2025;42(2):280-294
280-294
A Decrease in the Cognitive Status of Patients in the Long Term After Ischemic Stroke is Associated with the Levels of Adrenocorticotropic Hormone and Cortisol in the Hair
Resumo
Post-stroke cognitive impairment (PCN) is a common complication after ischemic stroke (IS). There is evidence that their development is largely due to regulatory and structural changes in neuroendocrine systems involved in the body’s adaptation to stress. Stress-related clinical and biochemical parameters were analyzed in 14 patients with normal cognitive status after AI, in 15 patients with mild cognitive impairment after AI, and in 10 people without stroke of the appropriate age and gender. The indicators were evaluated in the first days, a month later, six months later, and a year after AI. Using the logistic regression method, it was shown that a simultaneous decrease in the level of cortisol in hair and the level of adrenocorticotropic hormone (ACTH) in blood plasma six months after AI predicts a high probability of an unfavorable prognosis for the cognitive status of patients in the long term after a stroke. The data confirm previously obtained results indicating a significant contribution of stress-realizing systems in the development of post-stroke cognitive impairment.
Neurochemical Journal. 2025;42(2):295–304
295–304
The Cognitive Status of Patients After Ischemic Stroke is Associated with the Levels of Cytoplasmic Actin 1 and Some Immunoglobulins in Llcam-Positive Extracellular Vesicles of Blood Serum
Resumo
Post-stroke cognitive impairment is a significant contributor to disability in people who have had ischemic stroke. Previously, it was shown that the study of the composition of small extracellular vesicles and related functions provides new opportunities for diagnosing post-stroke cognitive impairment. The aim of this work was to compare the proteins of LICAM-positive extracellular vesicles of serum patients with different cognitive status in the acute period of IS. A comparative quantitative proteomic analysis of LICAM-positive extracellular vesicles of patients without cognitive impairment (8, mean age 61.8 ± 14.1 years) and patients with moderate cognitive impairment (MCI) (8, mean age 61.8 ± 14.1 years) revealed significant differences in the levels of 10 proteins out of 131 identified. Patients with MCI, compared to patients without MCI, had reduced levels of proteins associated with the immune system in the acute post-stroke period.
Neurochemical Journal. 2025;42(2):305-318
305-318