Increased dopamine transmission and adult neurogenesis in trace amine-associated receptor 5 (TAAR5) knockout mice

Efimova, Evgeniya V.; Kozlova, Alena A.; Разенкова, В. А.; Katolikova, N.; Antonova, Kristina A.; Sotnikova, Tatyana D.; Merkulyeva, Natalia; Veshchitskii, Aleksandr S.; Калинина, Дарья Сергеевна; Коржевский, Д. Э.; Musienko, Pavel; Kanov, Evgeny V.; Gainetdinov, Raul R.

doi:10.1016/j.neuropharm.2020.108373

Cited by 37 publications

(61 citation statements)

References 46 publications

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“…In humans, five out of six functional TAARs (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) are believed to serve similar olfactory functions [4]. However, there is recent evidence from the knockout mouse model that at least one member of this family, TAAR5, is expressed also in the limbic areas of the brain receiving projection from the olfactory system and involved in the regulation of monoamine transmission, emotional behaviors, and adult neurogenesis [5,6]. In fact, TAAR5 was first identified in 1998 as a putative neurotransmitter receptor (PNR) and its mRNA was found at low levels in several human brain areas, including the amygdala, the hippocampus, the caudate nucleus, the thalamus, the hypothalamus, and the substantia nigra [7].…”

Section: Introductionmentioning

confidence: 99%

Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis

Vaganova

Murtazina

Shemyakova

et al. 2021

IJMS

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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.

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Section: Introductionmentioning

confidence: 99%

Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis

Vaganova

Murtazina

Shemyakova

et al. 2021

IJMS

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“…Oscillations in the 0,5-4 Hz range are also considered to be a robust marker of dopamine depletion, particularly in basal ganglia, and correlate with motor dysfunction 44 . In case of TAAR5-KO mice, we have previously observed an increase in dopamine tissue levels in the striatum 25 , which could lead to a decrease in power of deltarange oscillations, as well as to a change in sensorimotor control and improvement of motor coordination in these mice.…”

Section: Discussionmentioning

confidence: 95%

“…Using LacZ labelling in TAAR5-KO mice we noted expression of the TAAR5 not only in the olfactory system 24 , limbic brain areas processing olfactory information 17 , and neurogenic zones 25 but also in the distinct motor centers of the brainstem and cerebellum.…”

Section: Discussionmentioning

confidence: 99%

“…As has been pointed out earlier 17 , we confirm here that TAAR5 (and likely TAARs in general) is not just ''an olfactory receptor'' involved in sensing innate odors 45 but is also involved in neuromodulation of sensorimotor controlin the brainstem, cerebellum and forebrain. Taking into account the specific effects in musculoskeletal systems as well as our previous finding of activation of adult neurogenesis 25 , we consider the potential utility of future TAAR5-based agents as an approach to pharmacotherapy of neuromotor disorders.…”

Section: Discussionmentioning

confidence: 99%

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Role of the Trace Amine Associated Receptors 5 (TAAR5) in Sensorimotor Functions

Калинина

Ptukha

Горяинова

et al. 2021

Preprint

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Monoamines are critical modulators of the sensorimotor neural networks. Using trace amine associated receptor 5 (TAAR5) knockout mice that express beta-galactosidase marker, we observed TAAR5 expression in the medial vestibular nucleus and Purkinje cells in the cerebellum suggesting that TAAR5 might be involved in gaze stabilization, vestibular and motor control. Accordingly, in various behavioral tests TAAR5-KO mice demonstrated lower endurance but better coordination and balance compared to wild type mice. Furthermore, we found specific changes in striatal local field potentials and motor cortex ECoG such as а decrease in delta andan increase in theta oscillations of power spectra respectively. The data obtained suggest that TAAR5 plays a considerable role in the regulation of postural stability, muscle force, balance and motor coordination during active movements, likely via modulation of monoaminergic systems on different levels of sensorimotor control, including brainstem, cerebellum and forebrain.

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“…Beta-galactosidase mapping of TAAR5 expression showed its localization not only in the glomeruli but also in deeper layers of olfactory bulb projecting to the limbic brain olfactory circuitry [ 15 ]. Moreover, TAAR5 knockout mice show increased adult neurogenesis and elevated number of dopamine neurons [ 16 ]. Thus, TAAR5 is emerging as a novel target for pharmacology and future TAAR5-based drugs may have the potential for the treatment of neuropsychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice

Zhukov

Kubarskaya

Karpova

et al. 2021

IJMS

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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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Increased dopamine transmission and adult neurogenesis in trace amine-associated receptor 5 (TAAR5) knockout mice

Cited by 37 publications

References 46 publications

Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis

Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis

Role of the Trace Amine Associated Receptors 5 (TAAR5) in Sensorimotor Functions

Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice

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