Classical monoamines are well-known modulators of sensorimotor neural networks. However, the role of trace amines and their receptors in sensorimotor function remains unexplored. Using trace amine-associated receptor 5 knockout (TAAR5-KO) mice, that express beta-galactosidase mapping its localization, we observed TAAR5 expression in the Purkinje cells of the cerebellum and the medial vestibular nucleus, suggesting that TAAR5 might be involved in the vestibular and motor control. Accordingly, in various behavioral tests, TAAR5-KO mice demonstrated lower endurance, but better coordination and balance compared to wild-type controls. Furthermore, we found specific changes in striatal local field potentials and motor cortex electrocorticogram, such as a decrease in delta and an increase in theta oscillations of power spectra, respectively. The obtained data indicate that TAAR5 plays a considerable role in regulation postural stability, muscle force, balance, and motor coordination during active movements, likely via modulation of monoaminergic systems at different levels of sensorimotor control involving critical brain areas such as the brainstem, cerebellum, and forebrain.

Trace amine-associated receptors (TAAR) recognize organic compounds, including primary, secondary, and tertiary amines. The TAAR5 receptor is known to be involved in the olfactory sensing of innate socially relevant odors encoded by volatile amines. However, emerging data point to the involvement of TAAR5 in brain functions, particularly in the emotional behaviors mediated by the limbic system which suggests its potential contribution to the pathogenesis of neuropsychiatric diseases. TAAR5 expression was explored in datasets available in the Gene Expression Omnibus, Allen Brain Atlas, and Human Protein Atlas databases. Transcriptomic data demonstrate ubiquitous low TAAR5 expression in the cortical and limbic brain areas, the amygdala and the hippocampus, the nucleus accumbens, the thalamus, the hypothalamus, the basal ganglia, the cerebellum, the substantia nigra, and the white matter. Altered TAAR5 expression is identified in Down syndrome, major depressive disorder, or HIV-associated encephalitis. Taken together, these data indicate that TAAR5 in humans is expressed not only in the olfactory system but also in certain brain structures, including the limbic regions receiving olfactory input and involved in critical brain functions. Thus, TAAR5 can potentially be involved in the pathogenesis of brain disorders and represents a valuable novel target for neuropsychopharmacology.

In the last two decades, interest has grown significantly in the investigation of the role of trace amines and their receptors in mammalian physiology and pathology. Trace amine-associated receptor 9 (TAAR9) is one of the least studied members of this receptor family with unidentified endogenous ligands and an unknown role in the central nervous system and periphery. In this study, we generated two new TAAR9 knockout (TAAR9-KO) rat strains by CRISPR-Cas9 technology as in vivo models to evaluate the role of TAAR9 in mammalian physiology. In these mutant rats, we performed a comparative analysis of a number of hematological and biochemical parameters in the blood. Particularly, we carried out a complete blood count, erythrocyte osmotic fragility test, and screening of a panel of basic biochemical parameters. No significant alterations in any of the hematological and most biochemical parameters were found between mutant and WT rats. However, biochemical studies revealed a significant decrease in total and low-density lipoprotein cholesterol levels in the blood of both strains of TAAR9-KO rats. Such role of TAAR9 in cholesterol regulation not only brings a new understanding of mechanisms and biological pathways of lipid exchange but also provides a new potential drug target for disorders involving cholesterol-related pathology, such as atherosclerosis.

Резюме MRSA представляет собой неоднородную группу в рамках вида Staphylococcus aureus. В составе данной группы выделяют, в зависимости от объекта паразитирования, три подгруппы: внутрибольничные варианты MRSA (hospital-associated MRSA, HA-MRSA), внебольничные MRSA (community-associated MRSA, CA-MRSA), MRSA, ассоциированные с сельскохозяйственными животными (livestock-associated MRSA, LA-MRSA), распространённые среди сельскохозяйственных животных. LA-MRSA широко распространены во многих странах. Существенной проблемой является распространение носительства LA-MRSA среди лиц, контактирующих с сельскохозяйственными животными. Взаимодействие популяций CA-MRSA и LA-MRSA приводит к получению LA-MRSA генов, ассоциированных с патогенностью для человека. В результате этого процесса возникают варианты LA-MRSA, способные распространяться среди людей. Эти стафилококки обладают способностью вызывать заболевания человека, в том числе внутрибольничные инфекции. Интенсификация животноводства, обусловливающая массовое и бесконтрольное применение антибиотиков, привела к формированию и повсеместному распространению LA-MRSA, характеризующегося, в отличие от CA-MRSA, множественной лекарственной резистентностью. Это обстоятельство делает практически невозможным элиминацию LA-MRSA из среды обитания человека и животных. Данное положение даёт основание признать, что одним из основных способов контроля за распространением LA-MRSA и вызываемых им заболеваний является мониторорование экологической, эпизоотической и эпидемиологической ситуаций среди поголовья сельскохозяйственных животных и населения.

Trace amine-associated receptors (TAARs) interact with amine compounds called “trace amines” which are present in tissues at low concentrations. Recently, TAARs expression in neoplastic tumors was reported. In this study, TAARs expression was analyzed in public RNAseq datasets in nevi and melanoma samples and compared to the expression of dopamine receptors (DRDs) that are known to be involved in melanoma pathogenesis. It was found that all DRDs and TAARs are expressed in nevi at comparable levels. Differential expression analysis demonstrated the drastic decrease of TAAR1, TAAR2, TAAR5, TAAR6, and TAAR8 expression in melanomas compared to benign nevi with only TAAR6, TAAR8, and TAAR9 remaining detectable in malignant tumors. No association of TAARs expression levels and melanoma clinicopathological characteristics was observed. TAARs co-expressed genes in melanoma and nevi were selected by correlation values for comparative pathway enrichment analysis between malignant and benign neoplasia. It was found that coexpression of TAARs with genes inquired in neurotransmitter signaling is lost in melanoma, and tumor-specific association of TAAR6 expression with the mTOR pathway and inflammatory signaling is observed. It is not excluded that TAARs may have certain functions in melanoma pathogenesis, the significance of which to tumor progression is yet to be understood.