TY - JOUR

T1 - Knocking Out TAAR5: A Pathway to Enhanced Neurogenesis and Dopamine Signaling in the Striatum

AU - Ваганова, Анастасия Николаевна

AU - Фесенко, Зоя Сергеевна

AU - Ефимова, Евгения Викторовна

AU - Чекрыгин, Сергей Алексеевич

AU - Шафранская, Дарья Дмитриевна

AU - Пржибельский, Андрей Дмитриевич

AU - Католикова, Наталия Викторовна

AU - Гайнетдинов, Рауль Радикович

PY - 2024/11/19

Y1 - 2024/11/19

N2 - 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.

AB - 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.

KW - Animals

KW - Corpus Striatum/metabolism

KW - Dopamine/metabolism

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Neurogenesis/genetics

KW - Receptors, G-Protein-Coupled/metabolism

KW - Signal Transduction

KW - Synapses/metabolism

KW - knockout

KW - TAAR5

KW - mice

KW - trace amine-associated receptors

KW - striatum

KW - medium spiny neurons

KW - neurogenesis

KW - astrocytes

KW - gene expression profiling

KW - dopamine

UR - https://www.mendeley.com/catalogue/8b9e39c5-339c-3e62-b922-0c498f2ee286/

U2 - 10.3390/cells13221910

DO - 10.3390/cells13221910

M3 - Article

C2 - 39594659

VL - 13

JO - Cells

JF - Cells

SN - 2073-4409

IS - 22

M1 - 1910

ER -