Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum

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 estima...

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Main Authors: Anastasia N. Vaganova, Zoia S. Fesenko, Evgeniya V. Efimova, Sergei A. Chekrygin, Daria D. Shafranskaya, Andrey D. Prjibelski, Nataliia V. Katolikova, Raul R. Gainetdinov
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Language:English
Published: MDPI AG 2024-11-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/22/1910
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author Anastasia N. Vaganova
Zoia S. Fesenko
Evgeniya V. Efimova
Sergei A. Chekrygin
Daria D. Shafranskaya
Andrey D. Prjibelski
Nataliia V. Katolikova
Raul R. Gainetdinov
author_facet Anastasia N. Vaganova
Zoia S. Fesenko
Evgeniya V. Efimova
Sergei A. Chekrygin
Daria D. Shafranskaya
Andrey D. Prjibelski
Nataliia V. Katolikova
Raul R. Gainetdinov
author_sort Anastasia N. Vaganova
collection DOAJ
description 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. Meanwhile, the upregulating effect of TAAR5 knockout on genes was associated with neurogenesis and synaptogenesis. The estimation of cell-type relative abundance through the deconvolution of RNA sequencing data demonstrated that TAAR5-KO striatum samples contain more D2 dopamine receptor-expressing medium spiny neurons but fewer astrocytes than wild-type mice. Our findings indicate that previously identified improvement in cognitive functions and motor coordination in TAAR5-KO mice may activate genes involved in neurogenesis, synaptogenesis, and synapse organization in the striatum. These data suggest that the pharmaceutical targeting of TAAR5 may improve striatum-dependent cognitive or motor functions. At the same time, a more detailed investigation of future TAAR5 antagonists’ effect on glia development is necessary.
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spelling doaj-art-52ed6ade49714c86ad072e23f20ca5fd2025-08-20T01:53:53ZengMDPI AGCells2073-44092024-11-011322191010.3390/cells13221910Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the StriatumAnastasia N. Vaganova0Zoia S. Fesenko1Evgeniya V. Efimova2Sergei A. Chekrygin3Daria D. Shafranskaya4Andrey D. Prjibelski5Nataliia V. Katolikova6Raul R. Gainetdinov7Institute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, RussiaInstitute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, RussiaInstitute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, RussiaResource Center “Bio-Bank Center”, Research Park of Saint-Petersburg State University, 198504 Saint-Petersburg, RussiaInstitute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, RussiaDepartment of Computer Science, University of Helsinki, 00014 Helsinki, FinlandInstitute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, RussiaInstitute of Translational Biomedicine, Saint-Petersburg State University, 199034 Saint-Petersburg, RussiaThe 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. Meanwhile, the upregulating effect of TAAR5 knockout on genes was associated with neurogenesis and synaptogenesis. The estimation of cell-type relative abundance through the deconvolution of RNA sequencing data demonstrated that TAAR5-KO striatum samples contain more D2 dopamine receptor-expressing medium spiny neurons but fewer astrocytes than wild-type mice. Our findings indicate that previously identified improvement in cognitive functions and motor coordination in TAAR5-KO mice may activate genes involved in neurogenesis, synaptogenesis, and synapse organization in the striatum. These data suggest that the pharmaceutical targeting of TAAR5 may improve striatum-dependent cognitive or motor functions. At the same time, a more detailed investigation of future TAAR5 antagonists’ effect on glia development is necessary.https://www.mdpi.com/2073-4409/13/22/1910trace amine-associated receptorsTAAR5striatumneurogenesisneurogenesisdopamine
spellingShingle Anastasia N. Vaganova
Zoia S. Fesenko
Evgeniya V. Efimova
Sergei A. Chekrygin
Daria D. Shafranskaya
Andrey D. Prjibelski
Nataliia V. Katolikova
Raul R. Gainetdinov
Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum
Cells
trace amine-associated receptors
TAAR5
striatum
neurogenesis
neurogenesis
dopamine
title Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum
title_full Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum
title_fullStr Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum
title_full_unstemmed Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum
title_short Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum
title_sort knocking out taar5 a pathway to enhanced neurogenesis and dopamine signaling in the striatum
topic trace amine-associated receptors
TAAR5
striatum
neurogenesis
neurogenesis
dopamine
url https://www.mdpi.com/2073-4409/13/22/1910
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