Trace amine-associated receptors (TAARs) are a group of G protein-coupled receptors that are expressed in the olfactory epithelium, central nervous system, and periphery. TAAR family generally consists of nine types of receptors (TAAR1-9), which can detect biogenic amines. During the last 5 years, the TAAR5 receptor became one of the most intriguing receptors in this subfamily. Recent studies revealed that TAAR5 is involved not only in sensing socially relevant odors but also in the regulation of dopamine and serotonin transmission, emotional regulation, and adult neurogenesis by providing significant input from the olfactory system to the limbic brain areas. Such results indicate that future antagonistic TAAR5-based therapies may have high pharmacological potential in the field of neuropsychiatric disorders. TAAR5 is known to be expressed in leucocytes as well. To evaluate potential hematological side effects of such future treatments we analyzed several hematological parameters in mice lacking TAAR5. In these mutants, we observed minor but significant changes in the osmotic fragility test of erythrocytes and hematocrit levels. At the same time, analysis of other parameters including complete blood count and reticulocyte levels showed no significant alterations in TAAR5 knockout mice. Thus, TAAR5 gene knockout leads to minor negative changes in the erythropoiesis or eryptosis processes, and further research in that field is needed. The impact of TAAR5 deficiency on other hematological parameters seems minimal. Such negative, albeit minor, effects of TAAR5 deficiency should be taken into account during future TAAR5-based therapy development.
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http://dx.doi.org/10.3390/ijms22147307 | DOI Listing |
Cells
November 2024
Institute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia.
The member of trace-amine associated receptor family, TAAR5 receptor was suggested to recognize tertiary amines, mostly in the olfactory system; however, knocking out the receptor TAAR5 in mice showed an enhancing effect on adult neurogenesis and dopamine neurotransmission in the striatum. To estimate the role of the TAAR5, we performed gene expression profiling of striatal samples from TAAR5 knockout (KO) mice and their wild-type littermates. The higher expression of several genes involved in dopaminergic signaling and the downregulation of genes associated with gliogenesis were revealed in TAAR5-KO mice.
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
October 2024
Mental Health Research Center, Moscow, Russia.
Objective: To evaluate the association of polymorphisms in the gene cluster on chromosome 6 with cognitive functions in patients with schizophrenia spectrum disorders and healthy controls.
Material And Methods: Patients with schizophrenia spectrum disorders (=216) and healthy people without a family history of mental disorders (=240) completed a battery of cognitive tests, from which individual indices of cognitive functioning were derived. Associations of the cognitive index with 22 polymorphisms in the genes were assessed using ANCOVA controlling for sex, age, genetic structure of the sample, and polygenic risk scores of schizophrenia and intelligence.
Int J Mol Sci
July 2024
Department of Pharmacy, Section of Medicinal Chemistry, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Benedetto XV, 3, 16132 Genoa, Italy.
G-protein-coupled receptors (GPCRs) represent a family of druggable targets when treating several diseases and continue to be a leading part of the drug discovery process. Trace amine-associated receptors (TAARs) are GPCRs involved in many physiological functions with TAAR1 having important roles within the central nervous system (CNS). By using homology modeling methods, the responsiveness of TAAR1 to endogenous and synthetic ligands has been explored.
View Article and Find Full Text PDFPharmacol Biochem Behav
September 2024
Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia; St. Petersburg University Hospital, St. Petersburg State University, 199034 St. Petersburg, Russia. Electronic address:
Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs.
View Article and Find Full Text PDFBiomedicines
June 2024
Institute of Translational Biomedicine, Saint-Petersburg State University, 199034 St. Petersburg, Russia.
Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side effects. In this regard, the search for and development of new antidepressant agents remains an urgent task.
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