Volume 111, Nº 5 (2025)

Here, we review current data that provide a basis for using the olfactory bulbectomy model as a model of mental disorders in humans. Based on extensive literature and our own data, we have shown the possibilities of using the olfactory bulbectomy model in rodents as a model of depression and Alzheimer's disease, taking into account the correspondence of the observed changes with modern criteria of validity. The removal of olfactory bulbs causes a complex of molecular, structural, and behavioral changes in animals, which cannot serve as an ideal model for certain disease. The review discusses the limitations of using this model and interpreting the results. Nevertheless, this model can be a useful tool for both basic and applied studies of brain pathologies, taking into account these limitations.

Disruptions in cerebral cortex development during early ontogenesis often lead to pharmacoresistant epilepsy and mental disorders. One such disruption is focal cortical dysplasia (FCD), which can be modeled in experimental animals by inducing cryogenic injury to the neocortex on the first day after birth. FCD is frequently associated with the development of epilepsy and behavioral impairments, such as deficits in learning, memory, and social interaction. These effects may be more pronounced when the brain is exposed to additional challenges, such as the combination of FCD with neonatal febrile seizures (FS). However, the specific characteristics of behavioral impairments in this combined pathology remain poorly understood. This study aimed to investigate behavioral impairments in adult male Wistar rats with FCD who had experienced FS. FCD was induced in rat pups on the first day of life (P0) by localized freezing of the somatosensory cortex. On the 10^th day of life (P10), FS were triggered in the rat pups through hyperthermia (exposure to warm air) for 30 minutes. Only animals with FS lasting at least 15 minutes were included in the study. The control group consisted of sham-operated rat pups that were separated from their mother for 30 minutes at P10 without exposure to heat. At 2–2.5 months of age, the animals' behavior was evaluated using the following tests: Open Field, Elevated Plus Maze, Social Interaction Test, and Spontaneous Alternation Test in the Y-Maze. The results revealed that the combination of FCD and FS in early life led to increased social activity and alterations in exploratory behavior and anxiety levels in adult rats. These findings suggest that the combined pathology selectively affects behavioral functions, potentially due to the reorganization of neural networks in the brain. The study expands our understanding of the consequences of FCD and FS on brain function development and highlights the need for further research into the mechanisms underlying these changes. This work may contribute to the development of new therapeutic strategies for patients with similar conditions.

This study investigated the long-term effects of assisted reproductive technologies (ART), i.e. in vitro embryo culture and embryo transfer, on behavior and brain development in B6.Cg-Tg mice, a model of Parkinson’s disease (PD), and wild-type C57BL/6 mice. Male offspring obtained using ART were compared with naturally conceived offspring. At six months of age, mice were assessed for anxiety in the elevated plus maze test; body and brain weights were measured as well. The results of the study demonstrated that naturally conceived B6.Cg-Tg mice exhibited lower anxiety levels and larger brain weights compared to wild-type mice. Using ART resulted in a decreased brain weight in B6.Cg-Tg offspring, as well as significantly decreased anxiety levels compared to the control groups. In wild-type C57BL/6 mice, ART did not cause significant changes in brain weight or anxiety levels. The results demonstrate effects of ART on behavior and brain development in offspring, particularly in those genetically predisposed to neurodegenerative diseases. These results demonstrate that further studies of the long-term effects of ART are warrant, particularly in the context of its impact on neurodevelopment and behavior, which has important medical implications.

Thyroid stimulating hormone (TSH) levels in autoimmune hypothyroidism and hypothyroidism caused by inactivating mutations in the TSH receptor are normal or elevated, which is due to increased thyroliberin (TRH)-stimulated TSH production in thyroid hormone (TH) deficiency. The main cause of hypothyroidism is a weakened thyroid response to TSH. This requires the development of approaches to increase the sensitivity of thyrocytes to TSH. One of them is the use of positive allosteric modulators (PAMs) of the TSH receptor, which enhance the effects of TSH on TH production. However, such PAMs are currently lacking. The aim of the work was to synthesize new thieno[2,3-d]-pyrimidine derivatives TPYox and TPYmp with PAM activity of the TSH receptor and to study their effects on basal and TRH-stimulated blood TH concentration and expression of genes involved in TH synthesis in the rat thyroid. When administered to rats, TPYox and TPYmp (20 mg/kg) had little effect on blood TH concentration and expression of TH synthesis genes, except for an increase in tT3 concentration and expression of the Dio2 gene encoding type 2 deiodinase when using TPYmp. At the same time, despite the absence of differences with the control, in the TPYox-treated group, the blood TH concentrations and the expression of the Tg, Tpo, Dio2, and Tshr genes decreased as compared to the TPYmp-treated rats, which we believe is due to the high reactivity of the oxirane cycle in TPYox and its inhibitory effect on some components of the thyroid system in the thyroid gland. Pretreatment of rats with TPYox and TPYmp preserved the stimulatory effects of TRH on TH concentration and thyroid gene expression, and in some cases significantly enhanced them. However, the dynamics and severity of the potentiating effect of TPYox and TPYmp differed. TPYox potentiated the stimulatory effects of TRH on blood tT4, fT3, and tT3 concentrations 1.5 h after TRH treatment, while TPYmp enhanced the stimulatory effects of TRH on fT3 and tT3 concentrations 3 h later, when the potentiating effect of TPYox had already disappeared. In the thyroid gland, TPYox enhanced TRH-induced Tpo gene expression, while TPYmp enhanced Dio2 and Nis gene expression. Based on the data obtained, it was concluded that the most promising drug for increasing the TSH receptor response to endogenous TSH is TPYmp, 5-amino-N-(tert-butyl)-4-{4-[3-(2-hydroxy-3-morpholinopropoxy)pro-1-yn-1-yl]phenyl}-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide, the first functionally active PAM of the TSH receptor that we developed.

The article presents experimental data obtained on isolated olfactory sensory neurons (OSN) of adult Wistar rats. The aim of the study was to show by in vivo fluorescent confocal microscopy using pharmacological analysis whether the GluN3A-subunit is localized in the olfactory sensory neurons of adult animals. Analysis of the results have revealed the presence of GluN3A-subunit in the OSN of adult rats as part of the excitatory glycine receptor and GluN3A containing N-methyl-D-aspartate receptor (GluN3A-NMDAR). In addition to them, the typical NMDAR and non-NMDAR are localized in the OSN. All these receptors can be located both in the same and in different receptor cells, which manifests the heterogeneity of the OSN in the olfactory epithelium.