Role of melanocortin system in the locomotor activity rhythms and melatonin secretion as revealed by agouti‐signalling protein (asip1) overexpression in zebrafish

Author:

Godino‐Gimeno Alejandra1,Leal Esther1,Chivite Mauro2,Tormos Elisabeth1,Rotllant Josep3,Vallone Daniela4,Foulkes Nicholas S.4,Míguez Jesús M.2,Cerdá‐Reverter Jose Miguel1ORCID

Affiliation:

1. Department of Fish Physiology and Biotechnology Instituto de Acuicultura de Torre de la Sal, IATS‐CSIC, Fish Neurobehaviour Lab Castellon Spain

2. Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía and Centro de Investigación Mariña Universidade de Vigo Vigo Spain

3. Department of Biotechnology and Aquaculture Instituto de Investigaciones Marinas, IIM‐CSIC Vigo Spain

4. Institute of Biological and Chemical Systems—Biological Information Processing (IBCS‐BIP), Department of Physiological Information Processing Karlsruhe Institute of Technology (KIT) Eggenstein‐Leopoldshafen Germany

Abstract

AbstractTemporal signals such as light and temperature cycles profoundly modulate animal physiology and behaviour. Via endogenous timing mechanisms which are regulated by these signals, organisms can anticipate cyclic environmental changes and thereby enhance their fitness. The pineal gland in fish, through the secretion of melatonin, appears to play a critical role in the circadian system, most likely acting as an element of the circadian clock system. An important output of this circadian clock is the locomotor activity circadian rhythm which is adapted to the photoperiod and thus determines whether animals are diurnal or nocturnal. By using a genetically modified zebrafish strain known as Tg (Xla.Eef1a1:Cau.asip1)iim04, which expresses a higher level of the agouti signalling protein 1 (Asip1), an endogenous antagonist of the melanocortin system, we observed a complete disruption of locomotor activity patterns, which correlates with the ablation of the melatonin daily rhythm. Consistent with this, in vitro experiments also demonstrated that Asip1 inhibits melatonin secretion from the zebrafish pineal gland, most likely through the melanocortin receptors expressed in this gland. Asip1 overexpression also disrupted the expression of core clock genes, including per1a and clock1a, thus blunting circadian oscillation. Collectively, these results implicate the melanocortin system as playing an important role in modulating pineal physiology and, therefore, circadian organisation in zebrafish.

Funder

Helmholtz-Fonds

Publisher

Wiley

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