Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep

IntroductionThis study aimed to investigate the role of TAAR2-9 in sleep/wake regulation, given TAAR1's known involvement in modulating neurotransmitter release and sleep patterns.MethodsMale TAAR2-9 knockout (KO) and wild-type (WT) mice were compared using baseline sleep/wake patterns, respons...

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Main Authors: Sunmee Park, Jasmine Heu, Gavin Scheldrup, Ryan K. Tisdale, Yu Sun, Meghan Haire, Shun-Chieh Ma, Marius C. Hoener, Thomas S. Kilduff
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Psychiatry
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Online Access:https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1467964/full
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author Sunmee Park
Jasmine Heu
Gavin Scheldrup
Ryan K. Tisdale
Yu Sun
Meghan Haire
Shun-Chieh Ma
Marius C. Hoener
Thomas S. Kilduff
author_facet Sunmee Park
Jasmine Heu
Gavin Scheldrup
Ryan K. Tisdale
Yu Sun
Meghan Haire
Shun-Chieh Ma
Marius C. Hoener
Thomas S. Kilduff
author_sort Sunmee Park
collection DOAJ
description IntroductionThis study aimed to investigate the role of TAAR2-9 in sleep/wake regulation, given TAAR1's known involvement in modulating neurotransmitter release and sleep patterns.MethodsMale TAAR2-9 knockout (KO) and wild-type (WT) mice were compared using baseline sleep/wake patterns, responses to sleep deprivation, effects of TAAR1 agonists, and dopaminergic markers. EEG recordings and tyrosine hydroxylase immunohistochemistry were used for analysis.ResultsKO mice exhibited lower delta and theta power and higher gamma power, with fragmented sleep characterized by 16% more NREM sleep during the dark phase and 23% more REM sleep during the light phase compared to WT mice. High doses of the TAAR1 agonist RO5256390 increased wakefulness and reduced NREM sleep, while both RO5256390 and the partial agonist RO5263397 suppressed REM sleep in KO mice. Elevated tyrosine hydroxylase levels in the ventral tegmental area suggested dopaminergic involvement in these altered sleep patterns.DiscussionTAAR2-9 modulates sleep/wake states and interacts with TAAR1. These findings highlight the therapeutic potential of targeting TAARs 2-9 in sleep-related neuropsychiatric disorders. Further research is needed to elucidate their roles.
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spelling doaj-art-fb4a167622a54378808e3d20f981abdf2025-01-29T06:46:20ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402025-01-011510.3389/fpsyt.2024.14679641467964Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleepSunmee Park0Jasmine Heu1Gavin Scheldrup2Ryan K. Tisdale3Yu Sun4Meghan Haire5Shun-Chieh Ma6Marius C. Hoener7Thomas S. Kilduff8Center for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesNeuroscience and Rare Diseases Discovery & Translational Area, Roche Pharma Research & Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.", Basel, SwitzerlandCenter for Neuroscience, Biosciences Division, SRI International, Menlo Park, CA, United StatesIntroductionThis study aimed to investigate the role of TAAR2-9 in sleep/wake regulation, given TAAR1's known involvement in modulating neurotransmitter release and sleep patterns.MethodsMale TAAR2-9 knockout (KO) and wild-type (WT) mice were compared using baseline sleep/wake patterns, responses to sleep deprivation, effects of TAAR1 agonists, and dopaminergic markers. EEG recordings and tyrosine hydroxylase immunohistochemistry were used for analysis.ResultsKO mice exhibited lower delta and theta power and higher gamma power, with fragmented sleep characterized by 16% more NREM sleep during the dark phase and 23% more REM sleep during the light phase compared to WT mice. High doses of the TAAR1 agonist RO5256390 increased wakefulness and reduced NREM sleep, while both RO5256390 and the partial agonist RO5263397 suppressed REM sleep in KO mice. Elevated tyrosine hydroxylase levels in the ventral tegmental area suggested dopaminergic involvement in these altered sleep patterns.DiscussionTAAR2-9 modulates sleep/wake states and interacts with TAAR1. These findings highlight the therapeutic potential of targeting TAARs 2-9 in sleep-related neuropsychiatric disorders. Further research is needed to elucidate their roles.https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1467964/fullTrace amine-associated receptorsTAAR2-9sleep regulationwakefulnessNREM sleepREM sleep
spellingShingle Sunmee Park
Jasmine Heu
Gavin Scheldrup
Ryan K. Tisdale
Yu Sun
Meghan Haire
Shun-Chieh Ma
Marius C. Hoener
Thomas S. Kilduff
Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep
Frontiers in Psychiatry
Trace amine-associated receptors
TAAR2-9
sleep regulation
wakefulness
NREM sleep
REM sleep
title Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep
title_full Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep
title_fullStr Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep
title_full_unstemmed Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep
title_short Trace amine-associated receptors (TAARs)2-9 knockout mice exhibit reduced wakefulness and disrupted REM sleep
title_sort trace amine associated receptors taars 2 9 knockout mice exhibit reduced wakefulness and disrupted rem sleep
topic Trace amine-associated receptors
TAAR2-9
sleep regulation
wakefulness
NREM sleep
REM sleep
url https://www.frontiersin.org/articles/10.3389/fpsyt.2024.1467964/full
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