Involvement of 5-HT3 and 5-HT4 Receptors in the Regulation of Circadian Clock Gene Expression in Mouse Small Intestine

Aoki, Natsumi; Watanabe, Hiroyuki; Okada, Ken-ichi; Aoki, Kazuya; Imanishi, Takuma; Yoshida, Daisuke; Ishikawa, Ryosuke; Shibata, Shigenobu

doi:10.1254/jphs.13253fp

Cited by 6 publications

(7 citation statements)

References 38 publications

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“…These results suggest that NRF may promote diurnal expression of intestinal clock genes and downstream clock-controlled genes through microbial-driven serotonin in growing rabbits. To further verify this hypothesis, a rhythmic addition of serotonin in vitro experiment was performed to reveal that serotonin can induce the diurnal expression of clock and tight junction genes in RIEC, and promote cell proliferation, which was consistent with previous findings (Aoki et al, 2014;Spohn et al, 2016). Thus, these results partially confirm that microbial-driven serotonin signals, as one of the zeitgebers, regulate clock gene expression in growing rabbit intestinal epithelial cells.…”

Section: Discussionsupporting

confidence: 86%

“…Body temperature, as an important zeitgeber, can activate cAMP-response element binding protein (CREB) through the Ca 2+ -CaM signaling pathway mediated by the temperature sensor TRPV4, thereby binding to the cAMP response element (CRE) located at the PER1/2 promoter and initiates gene expression (Buhr et al, 2010;Shibasaki et al, 2015). Similarly, serotonin activates CREB through G protein-coupled receptor-mediated cAMP-PKA signaling pathway, thereby initiating PER1/2 expression (Noda et al, 2004;Lee et al, 2010;Aoki et al, 2014). These results suggest that whether the microbial-driven serotonin is synchronized with the diurnal oscillations of body temperature may influence diurnal rhythmic expression of intestinal clock genes.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, Clostridium species is one of the main microbial flora in the intestine that contributes for the synthesis of more than 95% of serotonin by intestinal chromaffin cells (Yano et al, 2015). Moreover, it was confirmed that additional serotonin in vitro could increase the diurnal expression of PER1 and BMAL1 in peripheral tissues and suprachiasmatic nucleus through G protein-coupled receptor signaling pathways, and also promote proliferation of intestinal epithelial cells (Paulus and Mintz, 2012;Aoki et al, 2014;Yano et al, 2015;Moon et al, 2020). Notably, intestinal epithelial cells are renewed every 4-5 days.…”

Section: Introductionmentioning

confidence: 92%

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Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

Wang

Guo

Zhang

et al. 2021

Front. Cell. Infect. Microbiol.

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The circadian misalignment of the gut microbiota caused by unusual eating times in adult animals is related to disease development. However, whether the composition and diurnal rhythm of gut microbiota can be optimized by synchronizing the window period of eating with natural eating habits to reduce the risk of diarrhea remains unclear, especially in growing animals. In this study, 108 5-week-old weaned rabbits (nocturnal animals) were randomly subjected to daytime feeding (DF) and night-restricted feeding (NRF). At age 12 weeks, six rabbits were selected from each group, and caecum and cecal contents, as well as serum samples were collected at 4-h intervals during 24 h. Overall, NRF was found to reduce the risk of diarrhea in growing rabbits, improved the diurnal rhythm and abundance of beneficial microorganisms, along with the production of beneficial metabolites, whereas reduced the abundance of potential pathogens (Synergistes, Desulfovibrio, and Alistipes). Moreover, NRF improved diurnal rhythm of tryptophan hydroxylase isoform 1 and serotonin. Furthermore, NRF strengthened the diurnal amplitude of body core temperature, and promoted the diurnal expression of intestinal clock genes (BMAL1, CLOCK, REV-ERBα, and PER1), and genes related to the regulation of the intestinal barrier (CLAUDIN-1), and intestinal epithelial cell self-proliferation and renewal (BMI1). In vitro simulation experiments further revealed that synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, which are important zeitgebers, could promote the diurnal expression of clock genes and CLAUDIN-1 in rabbit intestinal epithelial cells (RIEC), and enhance RIEC proliferation. This is the first study to reveal that NRF reprograms the diurnal rhythm of the gut microbiome, promotes the diurnal expression of clock genes and tight junction genes via synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, thereby improving intestinal health and reducing the risk of diarrhea in growing rabbits. Collectively, these results provide a new perspective for the healthy feeding and management of growing animals.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

Wang

Guo

Zhang

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Ninety-five percent of 5-HT in the human body is distributed in the intestine and secreted by intestinal chromaffin cells . Dysregulation of intestinal flora can lower 5-HT levels and then affect the activity of the hypothalamus and other brain regions, eventually causing circadian disruption . Our results showed that GTP effectively ameliorate the disturbance of gut flora caused by circadian rhythm disorder.…”

Section: Discussionmentioning

confidence: 66%

Omics Analyses of Intestinal Microbiota and Hypothalamus Clock Genes in Circadian Disturbance Model Mice Fed with Green Tea Polyphenols

Zhang

Liu

et al. 2022

J. Agric. Food Chem.

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Green tea polyphenols (GTP) have similar activities as prebiotics, which effectively regulate the structure of intestinal flora and affect their metabolic pathways. The intestinal flora is closely related to the host’s circadian rhythm, and the supplementation with GTP may be an effective way to improve circadian rhythm disorders. In this study, we established a mouse model of circadian rhythm disturbance of anthropogenic flora to investigate the regulation mechanism of GTP on the host circadian rhythms. After 4 weeks of GTP administration, the results showed that GTP significantly alleviated the structural disorder of intestinal microbiota, thus effectively regulating related metabolites associated with brain nerves and circadian rhythms. Moreover, single-cell transcription of the mouse hypothalamus suggested that GTP up-regulated the number of astrocytes and oligodendrocytes and adjusted the expression of core clock genes Csnk1d, Clock, Per3, Cry2, and BhIhe41 caused by circadian disruption. Therefore, this study provided evidence that GTP can improve the physiological health of hosts with the circadian disorder by positively affecting intestinal flora and related metabolites and regulating circadian gene expression.

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“…Specific primer pairs (see Table 1) were designed using Primer3 Input (version 0.4.0). Real-time RT-PCR was executed under the following conditions: cDNA Synthesis at 42°C for 15 min, followed by 95°C for 2 min, PCR amplification for 40 cycles with denaturation at 95°C for 5 s, and annealing and extension at 60°C for 20 s (9). The relative levels of the target gene PCR product were normalized to those of 18S ribosomal RNA.…”

Section: Short Communicationmentioning

confidence: 99%

Effect of Quetiapine on Per1, Per2, and Bmal1 Clock Gene Expression in the Mouse Amygdala and Hippocampus

et al. 2014

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Abstract. Circadian rhythms are related to various psychiatric disorders. Recently, antipsychotics, including quetiapine (QTP), have been accepted as potential therapeutic agents for the treatment of depression, but its mechanism remains poorly understood. In this study, we examined clock gene fluctuation patterns in QTP-treated mice. QTP significantly increased Per2 mRNA at ZT12 and Per1 and Per2 expression at ZT18 in the amygdala. There were significant differences between the control and QTP groups in the cross-time effects of Per2 mRNA expression in the amygdala. Our findings suggest that QTP possibly acts on the circadian system, which then induces changes in mood symptoms.

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Involvement of 5-HT3 and 5-HT4 Receptors in the Regulation of Circadian Clock Gene Expression in Mouse Small Intestine

Abstract: Abstract. Several lines of evidence suggest that 5-HT receptors play a critical role in the expression of clock genes in the suprachiasmatic nucleus, the main circadian oscillator in hamsters.

Cited by 6 publications

References 38 publications

Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

Omics Analyses of Intestinal Microbiota and Hypothalamus Clock Genes in Circadian Disturbance Model Mice Fed with Green Tea Polyphenols

Effect of Quetiapine on Per1, Per2, and Bmal1 Clock Gene Expression in the Mouse Amygdala and Hippocampus

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