Daily rhythm and regulation of clock gene expression in the rat pineal gland

Simonneaux, Valérie; Poirel, Vincent‐Joseph; Garidou, Marie-Laure; Nguyen, Duong; Díaz‐Rodriguez, Esther; Pévet, Paul

doi:10.1016/j.molbrainres.2003.10.019

Cited by 61 publications

(80 citation statements)

References 40 publications

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“…The nocturnal increase of Per1 mRNA expression in the rat pineal is abolished by light exposure in the similar way as AA-NAT mRNA (Fukuhara et al, 2000;Simonneaux et al, 2004). It is indicated that both expressions are regulated by norepinepherine release from the SCN (Simonneaux et al, 2004). Taken together with the results reported here, this suggests that LL suppresses Per1 expression in vivo and that this effect is maintained in culture.…”

Section: Discussionsupporting

confidence: 82%

“…On the other hand, its rhythmicity in vivo must be rapidly damped by constant light, since after only one day of exposure its phase is robustly affected by culture time. The nocturnal increase of Per1 mRNA expression in the rat pineal is abolished by light exposure in the similar way as AA-NAT mRNA (Fukuhara et al, 2000;Simonneaux et al, 2004). It is indicated that both expressions are regulated by norepinepherine release from the SCN (Simonneaux et al, 2004).…”

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confidence: 72%

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Effects of Preparation Time on Phase of Cultured Tissues Reveal Complexity of Circadian Organization

Yoshikawa¹,

Yamazaki

Menaker

2005

J Biol Rhythms

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The phases of central (SCN) and peripheral circadian oscillators are held in specific relationships under LD cycles, but in the absence of external rhythmic input may damp or drift out of phase with each other. Rats exposed to prolonged constant light become behaviorally arrhythmic, perhaps as a consequence of dissociation of phases among SCN cells. We asked whether individual central and peripheral circadian oscillators were rhythmic in LL treated arrhythmic rats and, if rhythmic, what were the phase relationships among them. We prepared SCN, pineal gland, pituitary and cornea cultures from transgenic Per1-luc rats whose body temperature and locomotor activity were arrhythmic, and from several groups of rhythmic rats held in LD, DD, and short-term LL. We measured mPer1 gene expression by recording light output with sensitive photomultipliers. Most of the cultures from all groups displayed circadian rhythms. This could reflect persistent rhythmicity in vivo prior to culture, or, alternatively, rhythmicity that may have been initiated by the culture procedure. To test this we cultured tissues at two different times 12 h apart and asked whether phase of the rhythm was related to culture time. The pineal, pituitary and SCN cultures showed partial or complete dependence of phase on culture time, while peak phases of the cornea cultures were independent of culture time in rhythmic rats, and were randomly distributed regardless of culture time in arrhythmic animals. These results suggest that in behaviorally arrhythmic rats oscillators in the pineal, pituitary and SCN had been arrhythmic or severely damped in vivo while the cornea oscillator was free-running. The peak phases of the SCN cultures were particularly sensitive to some aspect of the culture procedure since rhythmicity of SCN cultures from robustly rhythmic LDentrained rats was strongly influenced when the procedure was carried out at any time except the second half of the day. Keywords circadian organization; Period1; constant light; suprachiasmatic nucleus; pineal; pituitary; cornea; culture While the molecular mechanisms that generate circadian oscillations within cells have been extensively studied (Reppert and Weaver 2002;Lowrey and Takahashi, 2004), understanding of the mechanisms that connect the molecular framework to physiological function and behavior is still limited (Buijs et al., 2003). We have approached these questions using a transgenic rat model carrying a luciferase gene under the control of the mouse Period1 (Per1) promoter. SCN cultures from these animals express circadian oscillations of Per1-luc expression indefinitely, while oscillations in cultured peripheral tissues damp after several cycles (Yamazaki et al., 2000). The phases of central and peripheral circadian oscillators are held in specific relationships under light-dark (LD) cycles (Yamazaki et al., 2000;Abe et al., 1 To whom correspondence should be addressed: Michael Menaker Department of Biology, University of Virginia, Charlottesville, VA 22903; Tel: 434-982-5767; F...

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 72%

Effects of Preparation Time on Phase of Cultured Tissues Reveal Complexity of Circadian Organization

Yoshikawa¹,

Yamazaki

Menaker

2005

J Biol Rhythms

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“…Previous studies have also shown that circadian clock genes, such as Period1, Cryptocrome, Bmal1 and Clock, are rhythmically expressed (Namihira, et al, 1999;Takekida et al, 2000;Fukuhara et al, 2002, Simonneaux et al, 2004. In our study we did not detect any circadian rhythm in the clock genes since most of these genes are not present on the Rat Genome U34A array GeneChip.…”

Section: Discussioncontrasting

confidence: 58%

Analysis of daily and circadian gene expression in the rat pineal gland

Fukuhara¹,

Tosini²

2008

Neuroscience Research

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The mammalian pineal gland is an important component of the circadian system. In the present study, we examined the expression of roughly 8000 genes in the rat pineal gland as a function of time of day under light-dark (LD) cycles and in constant dark (DD) using oligo DNA microarray technique. We identified 47 and 13 genes that showed higher levels at night and day, respectively, under LD. The same patterns of expression were also observed in DD. About half of the genes that peaked at night have a known biological function, i.e., transcription factors and proteins that are involved in signaling cascades, whereas 14 are expressed sequence tags and 8 have an unknown biological function. Twelve of the genes that are up-regulated at night were also up-regulated after 1 h NE stimulation, thus suggesting that the expression of these genes is controlled by adrenergic mechanisms. Of the 13 genes that were up-regulated in the daytime, 6 coded for proteins that are involved in intracellular signaling pathways. The results obtained with microarray analysis were well correlated with data obtained using real time quantitative RT-PCR. The present results provide new materials to dissect and understand the pineal physiology.

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“…5A). Likewise, an extra-SCN brain region (pineal gland) and a peripheral tissue (lung) known to contain circadian clocks (Sakamoto et al, 1998;Yamazaki et al, 2002;Karolczak et al, 2004;Simonneaux et al, 2004;Fukuhara et al, 2005) demonstrated an analogous effect of SP600125 (Table 1, Figs. 5B and 6A).…”

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confidence: 91%

c-Jun N-terminal kinase inhibitor SP600125 modulates the period of mammalian circadian rhythms

et al. 2007

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Circadian rhythms are endogenous cycles with periods close to, but not exactly equal to, 24 h. In mammals, circadian rhythms are generated in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as several peripheral cell types, such as fibroblasts. Protein kinases are key regulators of the circadian molecular machinery. We investigated the role of the c-Jun N-terminal kinases (JNK), which belong to the mitogen-activated protein kinases family, in the regulation of circadian rhythms. In rat-1 fibroblasts, the p46 kDa, but not the p54 kDa, isoforms of JNK expressed circadian rhythms in phosphorylation. The JNK-inhibitor SP600125 dose-dependently extended the period of Period1-luciferase rhythms in rat-1 fibroblasts from 24.23±0.17-31.48±0.07 h. This treatment also dose-dependently delayed the onset of the bioluminescence rhythms. The effects of SP600125 on explant cultures from Period1-luciferase transgenic mice and Period2 Luciferase knockin mice appeared tissue-specific. SP600125 lengthened the period in SCN, pineal gland, and lung explants in Period1-luciferase and Period2 Luciferase mice. However, in the kidneys circadian rhythms were abolished in Period1-luciferase, while circadian rhythms were not affected by SP600125 treatment in Period2 Luciferase mice. Valproic acid, already known to affect period length, enhanced JNK phosphorylation and, as predicted, shortened the period of the Period1-bioluminescence rhythms in rat-1 fibroblasts. In conclusion, our results showed that SP600125 treatment, as well as valproic acid, alters JNK phosphorylation levels, and modulates the period length in various tissues. We conclude that JNK phosphorylation levels may help to set the period length of mammalian circadian rhythms. Keywords SCN; peripheral oscillators; Period genes; valproic acid; real time bioluminescence monitoringDeveloped through evolution to adjust to environmental conditions, self-sustained circadian oscillators generate daily fluctuations in behavior and physiology with a period of approximately 24 h. The study of the mammalian circadian clock at molecular levels has progressed dramatically over the past decade (Fukuhara and Tosini, 2003;Schibler et al., 2003;Gachon et al., 2004). In mammals, the central circadian clock is localized to the suprachiasmatic nucleus (SCN) of the hypothalamus, which synchronizes circadian events within the body. Peripheral circadian clocks have been found in many types of cells and tissues, e.g. fibroblasts, pineal gland, heart, liver, kidney, lung, and so on. Sustained circadian rhythm can be generated not only in a SCN neuron, but also in a fibroblast and other tissues and organs. Numerous studies of the molecular clock mechanism have suggested that these circadian pacemakers consist of transcriptional/translational autoregulatory feedback loops of several clock gene products (Hastings and Herzog, 2004;Ko and Takahashi, 2006). The stability of clock proteins, regulated through phosphorylation and dephosphorylation via protein kinases and phosphatases, is ...

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Daily rhythm and regulation of clock gene expression in the rat pineal gland

Cited by 61 publications

References 40 publications

Effects of Preparation Time on Phase of Cultured Tissues Reveal Complexity of Circadian Organization

Effects of Preparation Time on Phase of Cultured Tissues Reveal Complexity of Circadian Organization

Analysis of daily and circadian gene expression in the rat pineal gland

c-Jun N-terminal kinase inhibitor SP600125 modulates the period of mammalian circadian rhythms

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