Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium

Abstract Many of the physiological, cellular, and molecular rhythms that are present within the eye are under the control of circadian clocks. Experimental evidence suggests that the retinal circadian clock, or its output signals (e.g., dopamine and melatonin), may contribute to eye disease and path...

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Autores principales: Kenkichi Baba, Jason P. DeBruyne, Gianluca Tosini
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:9a86b5ab9f60454b992b71fa807d3a562021-12-02T11:52:57ZDopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium10.1038/s41598-017-05394-x2045-2322https://doaj.org/article/9a86b5ab9f60454b992b71fa807d3a562017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05394-xhttps://doaj.org/toc/2045-2322Abstract Many of the physiological, cellular, and molecular rhythms that are present within the eye are under the control of circadian clocks. Experimental evidence suggests that the retinal circadian clock, or its output signals (e.g., dopamine and melatonin), may contribute to eye disease and pathology. We recently developed a retinal pigment ephithelium (RPE)-choroid preparation to monitor the circadian clock using PERIOD2 (PER2)::LUC knock-in mouse. In this study we report that dopamine, but not melatonin, is responsible for entrainment of the PER2::LUC bioluminescence rhythm in mouse RPE-choroid. Dopamine induced phase-advances of the PER2::LUC bioluminescence rhythm during the subjective day and phase-delays in the late subjective night. We found that dopamine acts exclusively through Dopamine 2 Receptors to entrain the circadian rhythm in PER2::LUC bioluminescence. Finallly, we found that DA-induced expression of core circadian clock genes Period1 and Period2 accompanied both phase advances and phase delays of the RPE-choroid clock, thus suggesting that – as in other tissues – the rapid induction of these circadian clock genes drives the resetting process. Since the RPE cells persist for the entire lifespan of an organism, we believe that RPE-choroid preparation may represent a new and unique tool to study the effects of circadian disruption during aging.Kenkichi BabaJason P. DeBruyneGianluca TosiniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kenkichi Baba
Jason P. DeBruyne
Gianluca Tosini
Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium
description Abstract Many of the physiological, cellular, and molecular rhythms that are present within the eye are under the control of circadian clocks. Experimental evidence suggests that the retinal circadian clock, or its output signals (e.g., dopamine and melatonin), may contribute to eye disease and pathology. We recently developed a retinal pigment ephithelium (RPE)-choroid preparation to monitor the circadian clock using PERIOD2 (PER2)::LUC knock-in mouse. In this study we report that dopamine, but not melatonin, is responsible for entrainment of the PER2::LUC bioluminescence rhythm in mouse RPE-choroid. Dopamine induced phase-advances of the PER2::LUC bioluminescence rhythm during the subjective day and phase-delays in the late subjective night. We found that dopamine acts exclusively through Dopamine 2 Receptors to entrain the circadian rhythm in PER2::LUC bioluminescence. Finallly, we found that DA-induced expression of core circadian clock genes Period1 and Period2 accompanied both phase advances and phase delays of the RPE-choroid clock, thus suggesting that – as in other tissues – the rapid induction of these circadian clock genes drives the resetting process. Since the RPE cells persist for the entire lifespan of an organism, we believe that RPE-choroid preparation may represent a new and unique tool to study the effects of circadian disruption during aging.
format article
author Kenkichi Baba
Jason P. DeBruyne
Gianluca Tosini
author_facet Kenkichi Baba
Jason P. DeBruyne
Gianluca Tosini
author_sort Kenkichi Baba
title Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium
title_short Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium
title_full Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium
title_fullStr Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium
title_full_unstemmed Dopamine 2 Receptor Activation Entrains Circadian Clocks in Mouse Retinal Pigment Epithelium
title_sort dopamine 2 receptor activation entrains circadian clocks in mouse retinal pigment epithelium
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/9a86b5ab9f60454b992b71fa807d3a56
work_keys_str_mv AT kenkichibaba dopamine2receptoractivationentrainscircadianclocksinmouseretinalpigmentepithelium
AT jasonpdebruyne dopamine2receptoractivationentrainscircadianclocksinmouseretinalpigmentepithelium
AT gianlucatosini dopamine2receptoractivationentrainscircadianclocksinmouseretinalpigmentepithelium
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