Vol 40, No 3 (2023)

Brain plasticity is a fundamental phenomenon based on various types of intercellular interactions (synaptic activity, neuritogenesis, synaptogenesis and elimination of synapses, neuron-glia interactions), development, differentiation, migration of newly-born cells and cell death (neurogenesis/gliogenesis and neuronal or glial cell death, angiogenesis and regression of cerebral microvessels), adaptation of tissue metabolism to changing environmental conditions. In this review, we discuss our own data and available literature in the context of regulation of certain types of energy metabolism (glycolysis, mitochondrial respiration) in neuronal, glial, and endothelial cells, the signaling functions of metabolites in nervous tissue, the mechanisms of establishment of cerebral insulin resistance, pseudohypoxia and associated neuroinflammation in brain pathology, as well as some prospects for detecting novel molecular markers of pathobiochemical processes associated with impaired metabolic plasticity in the developing and aging brain.

The current research is aimed to determine the long-term effects of the in vitro culture (IVC) and embryo transfer (ET) on the neonatal offspring development, as well as on the adult hippocampal neuronal densities, as well hippocampal neurogenesis in С57BL/6J mice. Offspring of naturally born C57BL/6J mice (C57BL group) were compared with C57BL/6J mice born as a result of the IVC combined with ET to C57BL/6J recipient females (ET-C57BL group). At age of 3 mo., no group differences were observed in the body weight and brain-to-body ratio, although sex differences in these variables were observed. The offspring of both sexes born after IVC-ET exhibited the lower level of neurogenesis in the dentate gyrus (DG) of the hippocampus as compared to the control C57BL group. To conclude, IVC and ET exerted no major effects on body and brain weight in offspring, but affected hippocampal neurogenesis in the adult offspring of both sexes. Besides, the number of pyramidal neurons in the CA3 area of hippocampus was lower in female offspring of ET-C57BL group.

According to the international organization Alzheimer’s Disease International (ADI), about 50 million people in the world suffer from Alzheimer’s disease (AD). However, there are no effective methods for preventing and slowing down the progression of AD. Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway is being discussed as an alternative way to prevent the development of AD and other neurodegenerative diseases. In the present study, we evaluated the ability of a recently synthesized selective JNK3 inhibitor, 11H‑indeno[1,2-b]quinoxalin-11-on oxime sodium (IQ-1S), to suppress neurodegenerative processes in OXYS rats at an early stage of development of signs of AD at the age of 4, 5 to 6 months. Treatment with IQ-1S (50 mg/kg intragastrically) led to the suppression of the development of neurodegenerative processes in the cerebral cortex of OXYS rats: an increase in the proportion of unchanged neurons, a decrease in the proportion of neurons with signs of destruction and irreversible damage, and a normalization of the glioneuronal index, which was facilitated by a decrease in the severity of hyperviscosity syndrome blood in OXYS rats. The use of the JNK3 inhibitor IQ-1S may be a promising strategy for the prevention of early neurodegenerative disorders and, possibly, the treatment of AD.

Activation of microglia, resident immune cells of the central nervous system, plays a key role in the pathogenesis of neurological disorders induced by infections, as well as traumatic and ischemic events. Understanding the responses of brain cells, primarily microglial cells, to damaging effects can help overcome their pathological consequences. In this work, we analyzed the cellular effects of bacterial lipopolysaccharide (LPS), which is widely used as a pro-inflammatory stimulus. The injection of LPS into the area of right striatum of rats caused a pronounced neurological deficit in a day, which was accompanied by an increase in the number of microglial cells, an increase in the density of glucocorticoid receptors (GR) and their translocation into the nuclei of cells co-expressing the executive protease of apoptosis, active caspase-3 and GR, in the area of LPS injection. The results indicate acute changes in the activity of microglial cells, as well as in the expression and functional activity of GR in response to bacterial endotoxin. Further elucidation of the functional role of active caspase-3 and GR in microglial cells under conditions of pro-inflammatory activation may help identify targets for alleviating the symptoms of a neurological disorder.

Depressive disorders and alcohol dependence are among the most common psychopathologies. It is known that disorders in the serotonergic and dopaminergic brain systems functioning lie in the pathogenesis of alcoholism and affective disorders. In this work, we studied the effects of prolonged administration of ethanol (1.5 g/kg, 20%, 10 days, i.p.) on behavior, functional activity of 5-HT1A and 5-HT2A receptors and expression of genes encoding serotonin (Htr1a, Htr2a) and dopamine (Drd1, Drd2) receptors in brain structures in mice of ASC strain (with the genetic predisposition to depressive-like behavior) and mice of the parental (“non-depressive”) CBA strain. It has been shown that alcoholization leads to an increase in motor activity in animals of both lines and an increase in the level of exploratory behavior in ASC mice. No significant effect of ethanol on social and depression-like behavior was found. The functional activities of 5-HT1A and 5-HT2A receptors (determined by the response to the administration of corresponding receptor agonists) were reduced by ethanol only in ASC animals. A decrease in 5-HT2A receptor gene expression was found in the frontal cortex of CBA mice treated with alcohol. At the same time, ethanol led to an increase in the mRNA levels of the 5-HT1A receptor gene in the striatum and the DRD1 receptor gene in the hypothalamus, as well as a decrease in the expression of the DRD2 receptor gene in the hippocampus of ASC mice. Thus, changes in the serotonergic and dopaminergic brain systems induced by chronic ethanol were more significant in ASC mice with a genetic predisposition to depression-like behavior.

We studied the role of polymorphisms rs1800629 of the TNF-α gene; rs4149584 of the TNFRSF1A gene; rs6074022, rs1883832, rs1535045, rs11086996 of the CD40 gene in the onset, clinical course and response to treatment in multiple sclerosis (MS) in a group of 152 patients, living in Tomsk region. 707 volunteers without autoimmune diseases and pathology of the nervous system were included in control group. The allele C of the rs6074022 polymorphism of CD40 gene was associated with the risk of MS and contributed to the high rate of disease progression. The T allele of the rs6074022 polymorphism of CD40 gene showed a significant association with the average rate of disease progression, and the GA genotype of rs1800629 polymorphism of TNF-α gene was associated with a higher frequency of MS exacerbations. Other polymorphisms did not demonstrate an association with both the risk of disease, the clinical features and response to treatment.