Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Szentirmai, Éva; Kapás, Levente; Krueger, James M.

doi:10.1152/ajpregu.00448.2006

Cited by 109 publications

(93 citation statements)

References 64 publications

(64 reference statements)

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“…The VMH contains ghrelin receptors (40,(46)(47)(48)(49), and ghrelin application increases the firing rate in a large proportion (Ϸ65%) of VMH neurons in young rats brain slices (Yanagida et al;50). Moreover, microinjection of ghrelin into the lateral hypothalamus, the medial preoptic area, or the paraventricular nucleus induces wakefulness and eating (51). Finally, ghrelin application to a brain slice phase shifts the suprachiasmatic nucleus (52).…”

Section: Summary Of Resultsmentioning

confidence: 99%

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

LeSauter

Hoque

Weintraub

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

281

269

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Increases in arousal and activity in anticipation of a meal, termed “food anticipatory activity” (FAA), depend on circadian food-entrainable oscillators (FEOs), whose locations and output signals have long been sought. It is known that ghrelin is secreted in anticipation of a regularly scheduled mealtime. We show here that ghrelin administration increases locomotor activity in nondeprived animals in the absence of food. In mice lacking ghrelin receptors, FAA is significantly reduced. Impressively, the cumulative rise of activity before food presentation closely approximates a Gaussian function ( r = 0.99) for both wild-type and ghrelin receptor knockout animals, with the latter having a smaller amplitude. For both groups, once an animal begins its daily anticipatory bout, it keeps running until the usual time of food availability, indicating that ghrelin affects response threshold. Oxyntic cells coexpress ghrelin and the circadian clock proteins PER1 and PER2. The expression of PER1, PER2, and ghrelin is rhythmic in light–dark cycles and in constant darkness with ad libitum food and after 48 h of food deprivation. In behaviorally arrhythmic-clock mutant mice, unlike control animals, there is no evidence of a premeal decrease in oxyntic cell ghrelin. Rhythmic ghrelin and PER expression are synchronized to prior feeding, and not to photic schedules. We conclude that oxyntic gland cells of the stomach contain FEOs, which produce a timed ghrelin output signal that acts widely at both brain and peripheral sites. It is likely that other FEOs also produce humoral signals that modulate FAA.

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Section: Summary Of Resultsmentioning

confidence: 99%

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

LeSauter

Hoque

Weintraub

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

281

269

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“…Intrahypothalamic ghrelin increases feeding and wakefulness in rats (100). In a patient with night-eating syndrome, nocturnal ghrelin levels appeared to be elevated (101).…”

Section: Lithiummentioning

confidence: 90%

Psychotropic medications affecting biological rhythm

Oral¹,

Özcan²,

Güleç³

et al. 2011

JMOOD

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Biyolojik ritmi etkileyen psikotrop ilaçlarBirçok canlı organizmada, omurgalı ve memeli canlıda olduğu gibi insanda da biyolojik işlevler çeşitli aralıklarla salınan ritimlerle yürür. Sirkadyen, ultradien ve infradian ya da daha uzun aralıklarla salınan iç ritimlerimiz kendi iç düzenlerini her şartta devam ettiren, bağımsız biyolojik organizasyonlardır. Biyolojik olarak kendiliğinden işleyen, istikrarlı bir yol varsa da, gerek psikiyatrik hastalıklar ve gerekse de psikotrop ilaçlar bu iç ritimleri değiştirebilir. Psikotrop ilaçlar, etki düzeneklerindeki nörotransmmitter ya da nöromediatörler vasıtasıyla doğrudan veya daha uzun vadede hormonal ya da genetik değişikliklere neden olarak da biyolojik ritimler üzerine etkili olabilir. Biyolojik ritim düzensizliklerinin duygudurum bozuklukları açısından hem neden hem de sonuç olarak önemine dikkat çeken birçok çalışma vardır. Duygudurum bozukluklarının takip ve tedavisinde psikofarmakolojik ajanların biyolojik ritimlere olan muhtemel etkisi de değerlendirilmesi önemlidir.

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“…Ghrelin stimulates GH secretion and promotes wakefulness, weight gain, and adrenocorticotropic hormone and cortisol release in humans and rodents (Frieboes et al, 1995;Wren et al, 2000;Diano et al, 2006;Szentirmai et al, 2007). Peripheral ghrelin levels rise sharply before main meals and decrease once the animal has been fed, most strikingly under restricted feeding conditions (Sugino et al, 2002;Kalra et al, 2003;Bodosi et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin Effects on the Circadian System of Mice

Yannielli

Molyneux²,

Harrington³

et al. 2007

J. Neurosci.

119

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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 ϳ3 h phase advance. In addition, ghrelin phase advanced the rhythm of PER2::LUC (Period2::Luciferase) expression in cultured SCN explants from mPer2Luc 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.

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Ghrelin microinjection into forebrain sites induces wakefulness and feeding in rats

Cited by 109 publications

References 64 publications

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

Stomach ghrelin-secreting cells as food-entrainable circadian clocks

Psychotropic medications affecting biological rhythm

Ghrelin Effects on the Circadian System of Mice

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