In mammals, the circadian and stress systems (both centers of which are located in the hypothalamus) are involved in adaptation to predictable and unpredictable environmental stimuli, respectively. Although the interaction and relationship between these two systems are intriguing and have been studied in different ways since the "pre-clock gene" era, the molecular interaction between them remains largely unknown. Here, we show by systematic molecular biological analysis that acute physical stress elevated only Period1 (Per1) mRNA expression in mouse peripheral organs. Although behavioral rhythms in vivo and peripheral molecular clocks are rather stable against acute restraint stress, the results of a series of promoter analyses, including chromatin immunoprecipitation assays, indicate that a glucocorticoid-responsive element in the Per1 promoter is indispensable for induction of this mRNA both in vitro and in vivo. These results suggest that Per1 can be a potential stress marker and that a third pathway of Per1 transcriptional control may exist in addition to the clock-regulated CLOCK-BMAL1/E-box and light-responsive cAMP-responsive element-binding protein/cAMP-responsive element pathways.
"Interestingly, Period family seems to be the most sensitive target to different signals in the molecular hepatic oscillator, as far as all the hormones studied to date in goldfish modifies Period transcripts (Fig. 3; Nisembaum et al., 2014a; own data presented in the XIII Congress of the European Biological Rhythms Society). In mammals, Per1 has different regulator elements on its promoter (CRE, E-box, GRE sequences; Vatine et al., 2011; Yamamoto et al., 2005), that supports their high sensitivity to different signals, and point out that Per genes family plays a key role integrating environmental and endogenous signals in the circadian system functional organization in fish. This agrees with the suggested mechanism for circadian synchronization to different environmental cues in mammals (Albrecht, 2012), and raises the question of two different types of oscillators, the light entrained oscillators and food entrained oscillators. "
"essful situation . Since peripheral organs express GC receptors ( GR ) that stimulate the transcription of the canonical clock genes Period ( Per ) 1 and Per2 after binding of GC , acute stress may shift the peripheral clocks so that these can respond quickly and properly to the stressful situation ( Balsalobre et al . , 2000 , So et al . , 2009 , Yamamoto et al . , 2005 ) . In contrast , the SCN belongs to those rare areas that do not express GR ; implying that the master clock maintains its intrinsic rhythm properties independent of GC signaling ( Balsalobre et al . , 2000 ) . Therefore , short - term stress is most likely not capable of perturbing the master clock and , thus , the SCN can reset the p"
[Show abstract][Hide abstract] ABSTRACT: We have recently demonstrated that the outcome of repeated social defeat (SD) on behavior, physiology and immunology is more negative when applied during the dark/active phase as compared with the light/inactive phase of male C57BL/6 mice. Here, we investigated the effects of the same stress paradigm, which combines a psychosocial and novelty stressor, on the circadian clock in transgenic PERIOD2::LUCIFERASE (PER2::LUC) and wildtype (WT) mice by subjecting them to repeated SD, either in the early light phase (social defeat light = SDL) or in the early dark phase (social defeat dark = SDD) across 19 days. The PER2::LUC rhythms and clock gene mRNA expression were analyzed in the suprachiasmatic nucleus (SCN) and the adrenal gland, and PER2 protein expression in the SCN was assessed. SDD mice showed increased PER2::LUC rhythm amplitude in the SCN, reduced Per2 and Cryptochrome1 mRNA expression in the adrenal gland, and increased PER2 protein expression in the posterior part of the SCN compared with single-housed control (SHC) and SDL mice. In contrast, PER2::LUC rhythms in the SCN of SDL mice were not affected. However, SDL mice exhibited a 2-hour phase advance of the PER2::LUC rhythm in the adrenal gland compared to SHC mice. Furthermore, plasma levels of brain-derived neurotrophic factor (BDNF) and BDNF mRNA in the SCN were elevated in SDL mice. Taken together, these results show that the SCN molecular rhythmicity is affected by repeated SDD, but not SDL, while the adrenal peripheral clock is influenced mainly by SDL. The observed increase in BDNF in the SDL group may act to protect against the negative consequences of repeated psychosocial stress.
Chronobiology International 07/2014; 31(9):1-12. DOI:10.3109/07420528.2014.940085 · 3.34 Impact Factor
"This also occurs for other hormones that are candidates to act as ''internal zeitgebers'' in some mammalian species (Albrecht, 2012; Dickmeis et al., 2013). The most studied are glucocorticoids, that in mammals synchronize peripheral oscillators (Dickmeis et al., 2013) probably via Per1 induction (Yamamoto et al., 2005). "
[Show abstract][Hide abstract] ABSTRACT: Ghrelin is a potent orexigenic signal mainly synthesized in the stomach and foregut of vertebrates. Recent studies in rodents point out that ghrelin could also act as an input for the circadian system and/or as an output of peripheral food-entrainable oscillators, being involved in the food anticipatory activity (FAA). In this study we pursue the possible interaction of ghrelin with the circadian system in a teleost, the goldfish (Carassius auratus). First, we analyzed if ghrelin is able to modulate the core clock functioning by regulating clock gene expression in fish under a light/dark cycle 12L:12D and fed at 10 am. As expected the acute intraperitoneal (IP) injection of goldfish ghrelin (gGRL[1-19], 44 pmol/g bw) induced the expression of hypothalamic orexin. Moreover, ghrelin also induced (∼2 fold) some Per clock genes in hypothalamus and liver. This effect was partially counteracted in liver by the ghrelin antagonist ([D-Lys(3)]-GHRP-6, 100 pmol/g bw). Second, we investigated if ghrelin is involved in daily FAA rhythms. With this aim locomotor activity was studied in response to IP injections (5-10 days) of gGRL[1-19] and [D-Lys(3)]-GHRP-6 at the doses above indicated. Ghrelin and saline injected fish showed similar 24 h activity patterns. However, ghrelin antagonist treatment abolished the FAA in schedule fed fish under 24 h light, suggesting the involvement of the endogenous ghrelin system in this pre-feeding activity. Altogether these results suggest that ghrelin could be acting as an input for the entrainment of the food-entrainable oscillators in the circadian organization of goldfish.
General and Comparative Endocrinology 03/2014; 205. DOI:10.1016/j.ygcen.2014.03.016 · 2.47 Impact Factor
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