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ID 114495
Title Alternative
Histone Methylation/Demethylation Inhibition Modulates Sleep
Author
Murillo-Rodríguez, Eric Universidad Anáhuac Mayab|Intercontinental Neuroscience Research Group
Arankowsky-Sandoval, Gloria Universidad Autónoma de Yucatán
Barros, Jorge Aparecido Intercontinental Neuroscience Research Group|Dom Bosco Catholic University
Rocha, Nuno Barbosa Intercontinental Neuroscience Research Group|Polytechnic Institute of Porto
Yamamoto, Tetsuya Intercontinental Neuroscience Research Group|Tokushima University Tokushima University Educator and Researcher Directory
Machado, Sérgio Intercontinental Neuroscience Research Group|Salgado de Oliveira University
Budde, Henning Intercontinental Neuroscience Research Group|Medical School Hamburg|Lithuanian Sports University
Telles-Correia, Diogo Intercontinental Neuroscience Research Group|University of Lisbon
Monteiro, Diogo Intercontinental Neuroscience Research Group|Sport Science School of Rio Major-Polytechnic Institute of Santarém|Research Center in Sport, Health and Human Development
Cid, Luis Intercontinental Neuroscience Research Group|Sport Science School of Rio Major-Polytechnic Institute of Santarém|Research Center in Sport, Health and Human Development
Veras, André Barciela Intercontinental Neuroscience Research Group|Dom Bosco Catholic University
Keywords
adenosine
dopamine
histone demethylation
serotonin
sleep
wakefulness
Content Type
Journal Article
Description
Histone methylation/demethylation plays an important modulatory role in chromatin restructuring, RNA transcription and is essential for controlling a plethora of biological processes. Due to many human diseases have been related to histone methylation/demethylation, several compounds such as 3-deazaneplanocin A (DZNep) or 3-((6-(4,5-Dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoic acid; N-[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-4-pyrimidinyl]-b-Alanine (GSK-J1), have been designed to inhibit histone methylase or suppress histone demethylase, respectively. In the present study, we investigated the effects on the sleep-wake cycle and sleep-related neurochemical levels after systemic injections of DZNep or GSK-J1 given during the light or dark phase in rats. DZNep dose-dependently (0.1, 1.0, or 10 mg/kg, i.p.) prolonged wakefulness (W) duration while decreased slow wave sleep (SWS) and rapid eye movement sleep (REMS) time spent during the lights-on period with no changes observed in dark phase. In opposite direction, GSK-J1 (0.1, 1.0, or 10 mg/kg, i.p.) injected at the beginning of the lights-on period induced no statistical changes in W, SWS, or REMS whereas if administered at darkness, we found a diminution in W and an enhancement in SWS and REMS. Finally, brain microdialysis experiments in freely moving animals were used to evaluate the effects of DZNep or GSK-J1 treatments on contents of sleep-related neurochemicals. The results showed that DZNep boosted extracellular levels of dopamine, norepinephrine, epinephrine, serotonin, adenosine, and acetylcholine if injected at the beginning of the lights-on period whereas GSK-J1 exerted similar outcomes but when administered at darkness. In summary, DZNep and GSK-J1 may control the sleep-wake cycle and sleep-related neurochemicals through histone methylation/demethylation activity.
Journal Title
Frontiers in Neuroscience
ISSN
1662453X
Publisher
Frontiers Media S.A.
Volume
13
Start Page
237
Published Date
2019-03-15
Rights
Copyright © 2019 Murillo-Rodríguez, Arankowsky-Sandoval, Barros, Rocha, Yamamoto, Machado, Budde, Telles-Correia, Monteiro, Cid and Veras. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). (https://creativecommons.org/licenses/by/4.0/) The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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language
eng
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departments
Integrated Arts and Sciences