Effect of alpha-NETA on auditory event related potentials in sensory gating study paradigm in mice

Aa, Aleksandrov; Dmitrieva, E. S.; Volnova, Anna; Knyazeva, Veronika M.; Polyakova, N. V.; Ptukha, Maria; Gainetdinov, Raul R.

doi:10.1016/j.neulet.2019.134470

Cited by 11 publications

(13 citation statements)

References 35 publications

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“…Results of animal studies indicate that TAAR5 might be involved in the pathogenesis of neuropsychiatric diseases. TAAR5-KO mice demonstrate anxiolytic/antidepressant-like phenotype [5]; at the same time animals treated with non-selective TAAR5 agonist α-NETA have disrupted synchronization of cortical gamma rhythms [22] and deregulated sensory gating [20,43] mirroring pathological changes in schizophrenia. Several studies included in the meta-analysis were devoted to demonstrating the transcriptome dis-balances in schizophrenia, bipolar disorder or major depressive disorder, but only one demonstrated significant downregulation of TAAR5 in the prefrontal cortex in major depressive disorder.…”

Section: Source Of Biasmentioning

confidence: 99%

“…These findings are not sufficient to fully appreciate TAAR5's functional significance as well as its potential involvement in the pathogenesis of neuropsychological diseases. At the same time, the evidence of the presence of TAAR5 in the human brain structures enables the translation of accumulating knowledge about the functional role of this receptor [6,[19][20][21][22]43] from model animals to humans.…”

Section: Source Of Biasmentioning

confidence: 99%

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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: Source Of Biasmentioning

confidence: 99%

Section: Source Of Biasmentioning

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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“…Apart from the endogenous agonist TMA that has a clear role in olfaction, only another putative agonist has been found and tested in animal models, namely α-NETA. Interestingly, in mice and rats, this compound was able to induce psychotic-like behavioral abnormalities, including features related to cognitive deficits present in psychotic patients [20,21]. How TAAR5 influences cognitive domains is still under investigation.…”

Section: Discussionmentioning

confidence: 99%

Improved Cognitive Performances in Trace Amine-Associated Receptor 5 (TAAR5) Knock-out Mice

Maggi¹,

Bon²,

Gustincich³

et al. 2022

Preprint

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Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

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“…Although with lower potencies, other two tertiary amines activate TAAR5, namely N-N-dimethylethylamine and N-methylpiperidine [5]. α-NETA, an inhibitor of acetyl-cholinesterase, potently activates TAAR5, and displays interesting in vivo properties in mice and rats, inducing psychotic-like states and influencing cortical parameters related to cognitive functions [25,26,[34][35][36].…”

Section: Discussionmentioning

confidence: 99%

“…Just two other TAAR5 agonists have been identified. α-NETA, which is known as an inhibitor of acetyl-cholinesterase, shows good activity in activating TAAR5 and has interesting in vivo properties in rodents, such as producing a behaviour consistent with psychosis-related cognitive deficits [25,26]. 3-iodothyronamine (T1AM), an endogenous derivative of the thyroid hormone, activates TAAR1, but at the same time, it behaves as an agonist and inverse agonist toward mTAAR5 and hTAAR5, respectively [17].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel Trace Amine-Associated Receptor 5 (TAAR5) Antagonists Using a Deep Convolutional Neural Network

Bon¹,

Chern²,

Cichero³

et al. 2022

Preprint

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Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to develop further more potent TAAR5 ligands with putative anxiolytic and antidepressant activity.

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Effect of alpha-NETA on auditory event related potentials in sensory gating study paradigm in mice

Cited by 11 publications

References 35 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

Improved Cognitive Performances in Trace Amine-Associated Receptor 5 (TAAR5) Knock-out Mice

Discovery of Novel Trace Amine-Associated Receptor 5 (TAAR5) Antagonists Using a Deep Convolutional Neural Network

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