Interacción entre el sistema endocrino y los osciladores circadianos en el carpín ("Carssius auratus"): regulación de genes reloj en relojes centrales y periféricos por péptidos de origen gastrointestinal y por glucocorticoides
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2017
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04/03/2016
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Universidad Complutense de Madrid
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Abstract
En la actualidad se considera el sistema circadiano de vertebrados como una red de osciladores que trabajan coordinadamente (Albrecht, 2012). Con respecto al carpín (Carassius auratus), especie de teleósteo objeto de la presente Tesis Doctoral, la localización de los osciladores endógenos que constituyen su sistema circadiano ha sido estudiada ampliamente por nuestro grupo de investigación mediante técnicas de PCR cuantitativa en tiempo real, demostrándose la expresión rítmica de genes reloj, componentes moleculares de los osciladores, en localizaciones encefálicas y periféricas (Feliciano et al., 2011; Nisembaum et al., 2012; Velarde et al., 2009). Sin embargo, hasta la fecha, no existe información sobre la localización anatómica de dichos osciladores en el carpín y apenas existen algunos estudios que lo muestren en otras especies teleósteos, estando todos ellos limitados al cerebro (pez cebra, Cermakian et al., 2000, Moore y Withmore, 2014, Weger et al., 2013, Ziv et al., 2005; trucha arcoíris, Mazurais et al., 2000; y Paralichthys olivaceus, Watanabe et al., 2012), sin abordar en ningún caso el estudio de la localización celular de los genes reloj en localizaciones periféricas. La comunicación entre osciladores es uno de los temas que suscita más interés en cronobiología en la actualidad y en este sentido, en los últimos años se ha descrito al hígado como uno de los osciladores endógenos más sensibles a diferentes señales rítmicas sistémicas y externas en mamíferos (Albrecht, 2012). Debido a que este órgano es uno de los principales responsables del metabolismo energético y reservas metabólicas (Schmutz et al., 2012), actualmente se está estudiando su papel en el contexto de la comunicación entre dicho metabolismo y el sistema circadiano. Además de las vías que transmiten la información lumínica a los osciladores periféricos como las de tipo nervioso, se ha propuesto que diversas señales hormonales serían responsables del mantenimiento y el correcto funcionamiento de los ritmos de los genes reloj en dichos osciladores, con especial relevancia en el hígado. Así, en mamíferos se ha demostrado que los componentes moleculares del oscilador hepático están regulados por determinadas señales hormonales como el glucagón (Sun et al., 2015) y los glucocorticoides (Balsalobre et al., 2000a; Fukuoka et al., 2005; Oishi et al., 2005; Reddy et al., 2007; Schmutz et al., 2012; Sujino et al., 2012; Yamamoto et al., 2005)...
Today, the vertebrate circadian system is considered as a network of oscillators that work together in a coordinated manner (Albrecht, 2012). With respect to goldfish (Carassius auratus), teleostean species object of the present PhD Thesis, the location of the endogenous circadian oscillators that constitute the system has been extensively studied by our research group using quantitative real-time PCR techniques, demonstrating the rhythmic expression of clock genes, molecular components of the oscillators, in brain and peripheral locations (Feliciano et al., 2011;. Nisembaum et al., 2012; Velarde et al., 2009). However, no information is available to date on the anatomical location of these oscillators in goldfish and, while there are a few studies reporting this aspect in other teleost species, all of them are limited to the brain (zebrafish (Danio rerio), Cermakian et al., 2000, Moore and Whitmore, 2014, Weger et al., 2013, Ziv et al., 2005;.. rainbow trout (Oncorhynchus mykiss), Mazurais et al., 2000; and Paralichthys olivaceus, Watanabe et al., 2012), without studying in any case the cellular localization of clock genes in peripheral locations. Communication between oscillators is one of the issues that raises more interest in chronobiology at present and in this sense, in recent years the liver has been described as one of the endogenous oscillators most sensitive to different systemic and external rhythmic signals in mammals (Albrecht, 2012). Given that this this organ is one of the main responsible for energy metabolism and metabolic reserves (Schmutz et al., 2012), its role in the context of communication between this metabolism and the circadian system is being currently studied. Thus, besides the pathways that transmit light information to peripheral oscillators such as the nervous communication, it has been proposed that various hormonal signals would be responsible for the maintenance and proper functioning of clock genes rhythms in these oscillators, with particular relevance in the liver...
Today, the vertebrate circadian system is considered as a network of oscillators that work together in a coordinated manner (Albrecht, 2012). With respect to goldfish (Carassius auratus), teleostean species object of the present PhD Thesis, the location of the endogenous circadian oscillators that constitute the system has been extensively studied by our research group using quantitative real-time PCR techniques, demonstrating the rhythmic expression of clock genes, molecular components of the oscillators, in brain and peripheral locations (Feliciano et al., 2011;. Nisembaum et al., 2012; Velarde et al., 2009). However, no information is available to date on the anatomical location of these oscillators in goldfish and, while there are a few studies reporting this aspect in other teleost species, all of them are limited to the brain (zebrafish (Danio rerio), Cermakian et al., 2000, Moore and Whitmore, 2014, Weger et al., 2013, Ziv et al., 2005;.. rainbow trout (Oncorhynchus mykiss), Mazurais et al., 2000; and Paralichthys olivaceus, Watanabe et al., 2012), without studying in any case the cellular localization of clock genes in peripheral locations. Communication between oscillators is one of the issues that raises more interest in chronobiology at present and in this sense, in recent years the liver has been described as one of the endogenous oscillators most sensitive to different systemic and external rhythmic signals in mammals (Albrecht, 2012). Given that this this organ is one of the main responsible for energy metabolism and metabolic reserves (Schmutz et al., 2012), its role in the context of communication between this metabolism and the circadian system is being currently studied. Thus, besides the pathways that transmit light information to peripheral oscillators such as the nervous communication, it has been proposed that various hormonal signals would be responsible for the maintenance and proper functioning of clock genes rhythms in these oscillators, with particular relevance in the liver...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, leída el 04-03-2016