The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats
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ORIGINAL INVESTIGATION
The retinoid X receptor: a nuclear receptor that modulates the sleep-wake cycle in rats Eric Murillo-Rodríguez 1,2 & Diana Millán-Aldaco 3 & Gloria Arankowsky-Sandoval 4 & Tetsuya Yamamoto 2,5 & Luis Cid 2,6,7 & Diogo Monteiro 2,6,7 & Nuno Barbosa Rocha 2,8 & Diogo Telles-Correia 2,9 & Diogo S. Teixeira 2,10,11 & André Barciela Veras 2,12 & Henning Budde 2,13 & Sérgio Machado 2,14 & Claudio Imperatori 2,15 & Pablo Torterolo 2,16 Received: 28 November 2019 / Accepted: 1 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. * Eric Murillo-Rodríguez [email protected] 1
Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico
2
Intercontinental Neuroscience Research Group, Mérida, Yucatán, Mexico
3
Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
4
Centro de Investigaciones Regionales “Dr. Hideyo Noguchi”, Universidad Autónoma de Yucatán, Mérid
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