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The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats

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Resumo:Rationale: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. Objectives: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. Methods: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. Results: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. Conclusions: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation.
Autores principais:Murillo-Rodríguez, Eric
Outros Autores:Millán-Aldaco, Diana; Arankowsky-Sandoval, Gloria; Yamamoto, Tetsuya; Cid, Luis; Monteiro, Diogo; Rocha, Nuno Barbosa; Telles-Correia, Diogo; Teixeira, Diogo S.; Veras, André Barciela; Budde, Henning; Machado, Sérgio; Imperatori, Claudio; Torterolo, Pablo
Assunto:Adenosine Dopamine Retinoid X receptor Serotonin Sleep
Ano:2020
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
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author Murillo-Rodríguez, Eric
author2 Millán-Aldaco, Diana
Arankowsky-Sandoval, Gloria
Yamamoto, Tetsuya
Cid, Luis
Monteiro, Diogo
Rocha, Nuno Barbosa
Telles-Correia, Diogo
Teixeira, Diogo S.
Veras, André Barciela
Budde, Henning
Machado, Sérgio
Imperatori, Claudio
Torterolo, Pablo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Murillo-Rodríguez, Eric
Millán-Aldaco, Diana
Arankowsky-Sandoval, Gloria
Yamamoto, Tetsuya
Cid, Luis
Monteiro, Diogo
Rocha, Nuno Barbosa
Telles-Correia, Diogo
Teixeira, Diogo S.
Veras, André Barciela
Budde, Henning
Machado, Sérgio
Imperatori, Claudio
Torterolo, Pablo
author_role author
contributor_name_str_mv Repositório Científico de Acesso Aberto da ULisboa
country_str PT
creators_json_txt [{\"Person.name\":\"Murillo-Rodríguez, Eric\"},{\"Person.name\":\"Millán-Aldaco, Diana\"},{\"Person.name\":\"Arankowsky-Sandoval, Gloria\"},{\"Person.name\":\"Yamamoto, Tetsuya\"},{\"Person.name\":\"Cid, Luis\"},{\"Person.name\":\"Monteiro, Diogo\"},{\"Person.name\":\"Rocha, Nuno Barbosa\"},{\"Person.name\":\"Telles-Correia, Diogo\",\"Person.identifier.orcid\":\"0000-0003-4217-2823\"},{\"Person.name\":\"Teixeira, Diogo S.\"},{\"Person.name\":\"Veras, André Barciela\"},{\"Person.name\":\"Budde, Henning\"},{\"Person.name\":\"Machado, Sérgio\"},{\"Person.name\":\"Imperatori, Claudio\"},{\"Person.name\":\"Torterolo, Pablo\"}]
datacite.contributors.contributor.contributorName.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
datacite.creators.creator.creatorName.fl_str_mv Murillo-Rodríguez, Eric
Millán-Aldaco, Diana
Arankowsky-Sandoval, Gloria
Yamamoto, Tetsuya
Cid, Luis
Monteiro, Diogo
Rocha, Nuno Barbosa
Telles-Correia, Diogo
Teixeira, Diogo S.
Veras, André Barciela
Budde, Henning
Machado, Sérgio
Imperatori, Claudio
Torterolo, Pablo
datacite.date.Accepted.fl_str_mv 2020-01-01T00:00:00Z
datacite.date.available.fl_str_mv 2022-06-06T15:21:39Z
datacite.date.embargoed.fl_str_mv 2022-06-06T15:21:39Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_16ec
datacite.subjects.subject.fl_str_mv Adenosine
Dopamine
Retinoid X receptor
Serotonin
Sleep
datacite.titles.title.fl_str_mv The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
dc.contributor.none.fl_str_mv Repositório Científico de Acesso Aberto da ULisboa
dc.creator.none.fl_str_mv Murillo-Rodríguez, Eric
Millán-Aldaco, Diana
Arankowsky-Sandoval, Gloria
Yamamoto, Tetsuya
Cid, Luis
Monteiro, Diogo
Rocha, Nuno Barbosa
Telles-Correia, Diogo
Teixeira, Diogo S.
Veras, André Barciela
Budde, Henning
Machado, Sérgio
Imperatori, Claudio
Torterolo, Pablo
dc.date.Accepted.fl_str_mv 2020-01-01T00:00:00Z
dc.date.available.fl_str_mv 2022-06-06T15:21:39Z
dc.date.embargoed.fl_str_mv 2022-06-06T15:21:39Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10451/53293
dc.language.none.fl_str_mv eng
dc.publisher.none.fl_str_mv Elsevier
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_16ec
dc.subject.none.fl_str_mv Adenosine
Dopamine
Retinoid X receptor
Serotonin
Sleep
dc.title.fl_str_mv The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description Rationale: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. Objectives: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. Methods: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. Results: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. Conclusions: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation.
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language eng
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oai_identifier_str oai:repositorio.ulisboa.pt:10451/53293
organization_str_mv urn:organizationAcronym:ul
person_str_mv Murillo-Rodríguez, Eric
Millán-Aldaco, Diana
Arankowsky-Sandoval, Gloria
Yamamoto, Tetsuya
Cid, Luis
Monteiro, Diogo
Rocha, Nuno Barbosa
Telles-Correia, Diogo
Telles-Correia, Diogo
https://www.ciencia-id.pt/B219-3860-D2C5
B219-3860-D2C5
http://orcid.org/0000-0003-4217-2823
0000-0003-4217-2823
Teixeira, Diogo S.
Veras, André Barciela
Budde, Henning
Machado, Sérgio
Imperatori, Claudio
Torterolo, Pablo
publishDate 2020
publisher.none.fl_str_mv Elsevier
reponame_str Repositório da Universidade de Lisboa
repository_id_str urn:repositoryAcronym:ul
service_str_mv urn:repositoryAcronym:ul
spelling engElsevierpt_PTRationale: The nuclear receptor retinoid X receptor (RXR) belongs to a nuclear receptor superfamily that modulates diverse functions via homodimerization with itself or several other nuclear receptors, including PPARα. While the activation of PPARα by natural or synthetic agonists regulates the sleep-wake cycle, the role of RXR in the sleep modulation is unknown. Objectives: We investigated the effects of bexarotene (Bexa, a RXR agonist) or UVI 3003 (UVI, a RXR antagonist) on sleep, sleep homeostasis, levels of neurochemical related to sleep modulation, and c-Fos and NeuN expression. Methods: The sleep-wake cycle and sleep homeostasis were analyzed after application of Bexa or UVI. Moreover, we also evaluated whether Bexa or UVI could induce effects on dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine contents, collected from either the nucleus accumbens or basal forebrain. In addition, c-Fos and NeuN expression in the hypothalamus was determined after Bexa or UVI treatments. Results: Systemic application of Bexa (1 mM, i.p.) attenuated slow-wave sleep and rapid eye movement sleep. In addition, Bexa increased the levels of dopamine, serotonin, norepinephrine epinephrine, adenosine, and acetylcholine sampled from either the nucleus accumbens or basal forebrain. Moreover, Bexa blocked the sleep rebound period after total sleep deprivation, increased in the hypothalamus the expression of c-Fos, and decreased NeuN activity. Remarkably, UVI 3003 (1 mM, i.p.) induced opposite effects in sleep, sleep homeostasis, neurochemicals levels, and c-Fos and NeuN activity. Conclusions: The administration of RXR agonist or antagonist significantly impaired the sleep-wake cycle and exerted effects on the levels of neurochemicals related to sleep modulation. Moreover, Bexa or UVI administration significantly affected c-Fos and NeuN expression in the hypothalamus. Our findings highlight the neurobiological role of RXR on sleep modulation.application/pdfpt_PTThe retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in ratsMurillo-Rodríguez, EricMillán-Aldaco, DianaArankowsky-Sandoval, GloriaYamamoto, TetsuyaCid, LuisMonteiro, DiogoRocha, Nuno BarbosaPersonalTelles-Correia, DiogoDSpacehttp://dspace.org/items/7eec6382-2f4a-45b0-b4be-7b6ac9a77786DSpacehttp://dspace.org/items/7eec6382-2f4a-45b0-b4be-7b6ac9a77786Telles-CorreiaDiogoCiência IDhttps://www.ciencia-id.ptB219-3860-D2C5ORCIDhttp://orcid.org0000-0003-4217-2823Scopus Author IDhttps://www.scopus.com15030253900Teixeira, Diogo S.Veras, André BarcielaBudde, HenningMachado, SérgioImperatori, ClaudioTorterolo, PabloHostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf0033-3158DOIIsPartOf10.1007/s00213-020-05518-82022-06-06T15:21:39Z20202020-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/53293http://purl.org/coar/access_right/c_16ecrestricted accessAdenosineDopamineRetinoid X receptorSerotoninSleep1865849 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/a9bddbf4-1d46-4624-be46-04c15c620763/downloadPsychopharmacology237720552073
spellingShingle The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
Murillo-Rodríguez, Eric
Adenosine
Dopamine
Retinoid X receptor
Serotonin
Sleep
status SINGLETON
subject.fl_str_mv Adenosine
Dopamine
Retinoid X receptor
Serotonin
Sleep
title The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
title_full The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
title_fullStr The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
title_full_unstemmed The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
title_short The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
title_sort The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
topic Adenosine
Dopamine
Retinoid X receptor
Serotonin
Sleep
topic_facet Adenosine
Dopamine
Retinoid X receptor
Serotonin
Sleep
url http://hdl.handle.net/10451/53293
visible 1