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Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status

2019-03-15Journal article Open access
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dc.contributor.authorMurillo-Rodríguez, Eric
dc.contributor.authorArankowsky-Sandoval, Gloria
dc.contributor.authorBarros, Jorge Aparecido
dc.contributor.authorRocha, Nuno Barbosa
dc.contributor.authorYamamoto, Tetsuya
dc.contributor.authorMachado, Sérgio
dc.contributor.authorBudde, Henning
dc.contributor.authorTelles-Correia, Diogo
dc.contributor.authorMonteiro, Diogo
dc.contributor.authorCid, Luis
dc.contributor.authorVeras, André Barciela
dc.date.accessioned2019-04-15T12:33:09Z
dc.date.available2019-04-15T12:33:09Z
dc.date.issued2019-03-15
dc.description.abstractHistone 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMurillo-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.2019.00237pt_PT
dc.identifier.doi10.3389/fnins.2019.00237pt_PT
dc.identifier.issn1662-453X
dc.identifier.urihttp://hdl.handle.net/10400.15/2508
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers in Neurosciencept_PT
dc.relationResearch Center in Sports Sciences, Health Sciences and Human Development
dc.relation.publisherversionhttps://www.frontiersin.org/articles/10.3389/fnins.2019.00237/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectadenosinept_PT
dc.subjectdopaminept_PT
dc.subjecthistone demethylationpt_PT
dc.subjectserotoninpt_PT
dc.subjectsleeppt_PT
dc.subjectwakefulnesspt_PT
dc.titleSleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Statuspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleResearch Center in Sports Sciences, Health Sciences and Human Development
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FDTP%2F04045%2F2019/PT
oaire.citation.conferencePlaceSuiçapt_PT
oaire.citation.endPage17pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleFrontiers in Neurosciencept_PT
oaire.citation.volume13pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameMonteiro
person.familyNameCid
person.givenNameDiogo
person.givenNameLuis
person.identifierF-1202-2015
person.identifier559047
person.identifier.ciencia-idED1F-6228-E26F
person.identifier.ciencia-idCE17-DDDC-86B2
person.identifier.orcid0000-0002-7179-6814
person.identifier.orcid0000-0001-8156-3291
person.identifier.ridK-3281-2012
person.identifier.scopus-author-id56437945500
person.identifier.scopus-author-id55507520600
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication6b2e136e-b810-49d4-964d-36c9537dcf83
relation.isAuthorOfPublicationf89cbc0e-02e0-4077-91a5-b35d685c68c3
relation.isAuthorOfPublication.latestForDiscoveryf89cbc0e-02e0-4077-91a5-b35d685c68c3
relation.isProjectOfPublication8ceabcc1-88fc-41fd-b0c0-70011e38d4e2
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