Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.15/2508 |
Resumo: | 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]-β-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. |
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Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Statusadenosinedopaminehistone demethylationserotoninsleepwakefulnessHistone 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]-β-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.Frontiers in NeuroscienceRepositório Científico do Instituto Politécnico de SantarémMurillo-Rodríguez, EricArankowsky-Sandoval, GloriaBarros, Jorge AparecidoRocha, Nuno BarbosaYamamoto, TetsuyaMachado, SérgioBudde, HenningTelles-Correia, DiogoMonteiro, DiogoCid, LuisVeras, André Barciela2019-04-15T12:33:09Z2019-03-152019-03-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.15/2508engMurillo-Rodriguez, E., Arankowsky-Sandoval, G., Barros, J., Rocha, N., Yamamoto,T., Machado, S., Budde, H., Telles-Correia, D., Monteiro, D., Cid, L., Veras, A. (2019). Sleep and neurochemical modulation by targeting the histone methylation/demethylation inhibition. Frontiers in Neuroscience, 13:237. doi: 10.3389/fnins.2019.002371662-453X10.3389/fnins.2019.00237info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-01-21T07:33:32Zoai:repositorio.ipsantarem.pt:10400.15/2508Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:54:32.037190Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
title |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
spellingShingle |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status Murillo-Rodríguez, Eric adenosine dopamine histone demethylation serotonin sleep wakefulness |
title_short |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
title_full |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
title_fullStr |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
title_full_unstemmed |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
title_sort |
Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status |
author |
Murillo-Rodríguez, Eric |
author_facet |
Murillo-Rodríguez, Eric Arankowsky-Sandoval, Gloria Barros, Jorge Aparecido Rocha, Nuno Barbosa Yamamoto, Tetsuya Machado, Sérgio Budde, Henning Telles-Correia, Diogo Monteiro, Diogo Cid, Luis Veras, André Barciela |
author_role |
author |
author2 |
Arankowsky-Sandoval, Gloria Barros, Jorge Aparecido Rocha, Nuno Barbosa Yamamoto, Tetsuya Machado, Sérgio Budde, Henning Telles-Correia, Diogo Monteiro, Diogo Cid, Luis Veras, André Barciela |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico de Santarém |
dc.contributor.author.fl_str_mv |
Murillo-Rodríguez, Eric Arankowsky-Sandoval, Gloria Barros, Jorge Aparecido Rocha, Nuno Barbosa Yamamoto, Tetsuya Machado, Sérgio Budde, Henning Telles-Correia, Diogo Monteiro, Diogo Cid, Luis Veras, André Barciela |
dc.subject.por.fl_str_mv |
adenosine dopamine histone demethylation serotonin sleep wakefulness |
topic |
adenosine dopamine histone demethylation serotonin sleep wakefulness |
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]-β-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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-04-15T12:33:09Z 2019-03-15 2019-03-15T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.15/2508 |
url |
http://hdl.handle.net/10400.15/2508 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Murillo-Rodriguez, E., Arankowsky-Sandoval, G., Barros, J., Rocha, N., Yamamoto,T., Machado, S., Budde, H., Telles-Correia, D., Monteiro, D., Cid, L., Veras, A. (2019). Sleep and neurochemical modulation by targeting the histone methylation/demethylation inhibition. Frontiers in Neuroscience, 13:237. doi: 10.3389/fnins.2019.00237 1662-453X 10.3389/fnins.2019.00237 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers in Neuroscience |
publisher.none.fl_str_mv |
Frontiers in Neuroscience |
dc.source.none.fl_str_mv |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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