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The Journal of Neuroscience, March 14, 2007, 27(11):2890-2895; doi:10.1523/JNEUROSCI.3913-06.2007

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Behavioral/Systems/Cognitive
Ghrelin Effects on the Circadian System of Mice

Paola C. Yannielli,¹  Penny C. Molyneux,² Mary E. Harrington,² and Diego A. Golombek¹

¹Universidad Nacional de Quilmes/Consejo Nacional de Investigaciones Científicas y Técnicas, Bernal, 1876 Buenos Aires, Argentina, and ²Neuroscience Program, Smith College, Northampton, Massachusetts 01063

Correspondence should be addressed to Dr. Diego Golombek, Universidad Nacional de Quilmes, Roque S. Peña 352 Bernal, 1876 Buenos Aires, Argentina. Email: dgolombek{at}unq.edu.ar

The orexigenic peptide ghrelin stimulates both food intake and growth hormone release and is synthesized in the stomach and in hypothalamic areas involved in feeding control. The suprachiasmatic nuclei of the hypothalamus (SCN) control most circadian rhythms, although there is evidence that some oscillators, such as food-entrainable oscillators, can drive activity rhythms even after SCN ablation. Ghrelin levels exhibit a circadian rhythm and closely follow feeding schedules, making this peptide a putative candidate for food-related entraining signals. We examined the response of the SCN to ghrelin treatments in vitro, by means of electrophysiological and bioluminescence recordings, and in vivo, by assessing effects on the phase of locomotor activity rhythms. Ghrelin applied at circadian time 6 in vitro to cultured SCN slices induced an 3 h phase advance. In addition, ghrelin phase advanced the rhythm of PER2::LUC (Period2::Luciferase) expression in cultured SCN explants from mPer2^Luc transgenic mice. In vivo, intraperitoneal administration of ghrelin or a synthetic analog, growth hormone-releasing protein-6 (GHRP-6), to ad libitum fed animals failed to alter circadian phase. When injected after 30 h of food deprivation, GHRP-6 induced a phase advance compared with saline-injected animals. These results indicate that ghrelin may play a role in the circadian system by exerting a direct action on the SCN and that the system as a whole may become sensitive to ghrelin and other feeding-related neuropeptides under conditions of food restriction.

Key words: ghrelin; phase shift; electrophysiology; bioluminescence; food entrainment; GHRP-6

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Received Sept. 8, 2006; revised Feb. 2, 2007; accepted Feb. 2, 2007.

Correspondence should be addressed to Dr. Diego Golombek, Universidad Nacional de Quilmes, Roque S. Peña 352 Bernal, 1876 Buenos Aires, Argentina. Email: dgolombek{at}unq.edu.ar

This article has been cited by other articles:

				J. M. Frecka and R. D. Mattes Possible entrainment of ghrelin to habitual meal patterns in humans Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G699 - G707. [Abstract] [Full Text] [PDF]

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