Nejrohimiâ

The 5-HT₇ receptor, one of the most recently discovered members of the serotonin receptor family, plays a pivotal role in regulating central nervous system processes. Over the past three decades, substantial research has provided insights into its gene, expression patterns, molecular structure, and pharmacological properties. The 5-HT₇ receptor is involved in thermoregulation, sleep, circadian rhythms, and mood regulation, attracting increasing attention as a promising target for the treatment of depressive disorders, Alzheimer’s disease, and Parkinson’s disease. In this review, based on a systematic analysis of publications from 1993–2024, with a predominant focus on studies from the last decade in PubMed, Scopus and Web of Science databases, we provide an in-depth discussion of the functional characteristics of the 5-HT₇ receptor, its pharmacological profile, and current hypothetical models and molecular interactions that enhance our understanding of its unique role in neurophysiological regulation. Special attention is given to the therapeutic potential of the 5-HT₇ receptor in neuropsychiatric and neurodegenerative diseases.

Immune dysregulation and inflammation play a key role in the pathogenesis of various affective disorders associated with excessive aggressiveness. Aggressive behavior formed in experimental models under influence of psychological stress or genetic factors is accompanied by changes in immune function, production of circulating cytokines, as well as temporal and region-dependent variations in their content within brain structures involved in behavior control and immunomodulation. Studying a role of neuroimmune interactions in the regulation of aggressive behavior is a fundamental challenge not only to advance our understanding of the neurobiological mechanisms underlying human aggression and violence, but also for developing effective approaches to its correction.

The hippocampus is one of the brain structures whose functions and morphology are impaired in depression. The fast-acting antidepressant ketamine reverses these impairments, but the mechanisms of its action are still not fully understood. Optogenetic stimulation of glutamatergic neurons in the CA1 region of the dorsal hippocampus of rats with the preliminary introduction of vectors expressing photosensitive channelrhodopsin led to the manifestation of a sign of depressive-like behavior – an increase in the time of immobility in the tail suspension test, compared to control animals. Immunohistochemical analysis of the expression of the early response protein c-Fos in the CA1 region of the hippocampus confirmed the activation of pyramidal neurons under the influence of light, revealing their involvement in the development of depressive-like behavior. Administration of a subanesthetic dose of ketamine prevented the manifestation of depressive-like behavior trait induced by optogenetic activation of glutamatergic neurons in the CA1 region of the dorsal hippocampus and abolished the increase in c-fos mRNA levels induced by optical stimulation. Thus, we demonstrated for the first time the ability of ketamine to reverse depressive-like behavior trait induced by optogenetic stimulation of the activity of dorsal hippocampal glutamatergic neurons. Overall, the results indicate the important role of dorsal hippocampal glutamatergic neurons in the regulation of psychoemotional behavioral responses and their sensitivity to ketamine administration.

Autism spectrum disorders (ASD) are the most common neurodevelopmental disorders, however, their mechanisms are still poorly understood. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are known as key players in the regulation of brain plasticity and behavior. Among the variety of 5-HT receptors, the most interesting is the 5-HT_1A receptor, which is the main regulator of the brain 5-HT system functioning. In this work, we investigated the effect of 5-HT_1A receptor overexpression in the frontal cortex induced by the administration of the adeno-associated virus pAAV-Syn-HTR1A-eGFP to BTBR T+ Itpr3tf/J (BTBR) mice, a model of autism, on autism-like behavior and on the expression of the Htr1a gene transcription factor – Freud-1 (encoded by the Cc2d1a gene), its intracellular signal transducer ERK1/2 (encoded by the Mapk3 gene), 5-HT₇ receptors, mature BDNF, proBDNF and TrkB and p75^NTR receptors. Overexpression of the 5-HT_1A receptor had no effect on time in the center and locomotor activity in the open field test, social behavior in the three-chamber test, immobility time in the tail suspension test, and associative learning in the “operant wall” paradigm, but it enhanced the severity of stereotyped behavior in the marble burying test. 5-HT_1A receptor overexpression in the frontal cortex did not affect the mRNA and protein levels of 5-HT₇ receptors, mature BDNF, proBDNF and TrkB and p75^NTR receptors in the cortex and hippocampus of BTBR mice. However, overexpression caused an increase in the protein level of the transcription factor Freud-1 in the hippocampus without changing the mRNA level of Cc2d1a in the frontal cortex and hippocampus. No changes in the pERK/ERK ratio were found in both investigated brain structures. Thus, the results of this study indicate a possible disruption in interactions of: 5-HT_1A receptors with downstream intracellular signal transducers; 5-HT system, BDNF and TrkB receptors; and 5-HT_1A and 5-HT₇ receptors in the frontal cortex of BTBR mice.

A special place in neurobiology is occupied by the study of glial activity during the development of central nervous system pathology. Debates about the dangers or benefits of glia have been ongoing, as well as the searching for ways to pharmacologically correct the glial activation pathways. It is steel remains unclear whether we should to completely disable glia from the regeneration process, or vice versa, activation of some glial functions is necessary. Vimentin, one of the structural components of the cytoskeleton, has been shown to reveal a dual functionality. Some studies demonstrates that, as a structural component of the glial scar, vimentin enhances the consolidation of the damaged area, preventing the axonal growth and the motor function restoration. Other researches, on the contrary, present vimentin as a secreted protein that has the abilities to attract the nerve fibers and promote the regeneration of damaged axons. To date the vimentin role in central nervous system (CNS) injuries has been described very poorly and the conclusions drawn are extremely contradictory. The purpose of this review is an attempt to summarize the recent studies results about the role of vimentin in modeling CNS damage.

Genetically encoded fluorescent proteins are widely used in biological research in general and in neurobiology in particular. When using these tools, it is important that the expression of the fluorescent protein does not disrupt the natural physiological processes in the cell. Addition of the farnesylation motif to fluorescent proteins leads to their anchoring in the plasma membrane, which is often used to visualize fine details of cell morphology, such as dendritic spines. In our work, we investigated the development of spines in primary cultured neocortical neurons by transfecting cells with farnesylated and unmodified EGFP by electroporation in suspension on the day of planting. It was found that neurons expressing farnesylated EGFP demonstrate pronounced disturbances in spine development, in particular, these cells were characterized by longer spines with more filopodia-like structures, which is typical for various pathological conditions. Therefore, when using farnesylated fluorescent proteins in experiments, it is necessary to take into account their possible negative impact on the development of various membrane structures of the cell, in particular neuronal spines.

According to the totality of inflammatory markers, a cluster of patients with autism spectrum disorders (ASD) and high levels of inflammation (N = 35, 70%) was identified. Discriminant analysis showed that the catabolite of the kynurenine pathway, which makes the greatest contribution to the pathogenesis of RAS, is quinolic acid. Dysregulation of energy metabolism has been revealed, including both the main pathways of catabolism (glycolysis, the Krebs cycle) and alternative pathways (beta-oxidation, ketogenesis, branched amino acid metabolism) with impaired mitochondrial function (meglutol) in patients with ASD. Correlations have been revealed for a number of energy exchange metabolites with indicators of inflammation. Inflammation in ASD is associated with dysregulation of energy metabolism and mitochondrial dysfunction. These data can serve as the basis for new treatment protocols, including anti-inflammatory therapy, metabolic correction, and restoration of mitochondrial function.