Circadian neurons in the paraventricular nucleus entrain and sustain daily rhythms in glucocorticoids

AbstractSignals from the central circadian pacemaker, the suprachiasmatic nucleus (SCN), must be decoded to generate daily rhythms in hormone release. Here, we hypothesized that the SCN entrains rhythms in the paraventricular nucleus (PVN) to time the daily release of corticosterone. In vivo recording revealed a critical circuit from SCN vasoactive intestinal peptide (SCNVIP)-producing neurons to PVN corticotropin-releasing hormone (PVNCRH)-producing neurons. PVNCRH neurons peak in clock gene expression around midday and in calcium activity about three hours later. Loss of the clock gene Bmal1 in CRH neurons results in arrhythmic PVNCRH calcium activity and dramatically reduces the amplitude and precision of daily corticosterone release. SCNVIP activation reduces (and inactivation increases) corticosterone release and PVNCRH calcium activity, and daily SCNVIP activation entrains PVN clock gene rhythms by inhibiting PVNCRH neurons. We conclude that daily corticosterone release depends on coordinated clock gene and neuronal activity rhythms in both SCNVIP and PVNCRH neurons.

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The mammalian circadian pacemaker regulates wakefulness via CRF neurons in the paraventricular nucleus of the hypothalamus

Science Advances ◽

10.1126/sciadv.abd0384 ◽

2020 ◽

Vol 6 (45) ◽

pp. eabd0384

Author(s):

Daisuke Ono ◽

Yasutaka Mukai ◽

Chi Jung Hung ◽

Srikanta Chowdhury ◽

Takashi Sugiyama ◽

...

Keyword(s):

Locomotor Activity ◽

Paraventricular Nucleus ◽

Gabaergic Neurons ◽

Corticotropin Releasing Factor ◽

Optical Manipulation ◽

Circadian Regulation ◽

Circadian Pacemaker ◽

Daily Rhythms ◽

Crf Neurons

In mammals, the daily rhythms of physiological functions are timed by the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Although the importance of the SCN for the regulation of sleep/wakefulness has been suggested, little is known about the neuronal projections from the SCN, which regulate sleep/wakefulness. Here, we show that corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus mediate circadian rhythms in the SCN and regulate wakefulness. Optogenetic activation of CRF neurons promoted wakefulness through orexin/hypocretin neurons in the lateral hypothalamus. In vivo Ca2+ recording showed that CRF neurons were active at the initiation of wakefulness. Furthermore, chemogenetic suppression and ablation of CRF neurons decreased locomotor activity and time in wakefulness. Last, a combination of optical manipulation and Ca2+ imaging revealed that neuronal activity of CRF neurons was negatively regulated by GABAergic neurons in the SCN. Our findings provide notable insights into circadian regulation of sleep/wakefulness in mammals.

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In vivo evaluation of the effect of lithium on peripheral circadian clocks by real-time monitoring of clock gene expression in near-freely moving mice

Scientific Reports ◽

10.1038/s41598-019-47053-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Yuka Sawai ◽

Takezo Okamoto ◽

Yugo Muranaka ◽

Rino Nakamura ◽

Ritsuko Matsumura ◽

...

Keyword(s):

Gene Expression ◽

Real Time ◽

Clock Gene ◽

Circadian Clocks ◽

Real Time Monitoring ◽

In Vivo Evaluation ◽

Clock Gene Expression ◽

Freely Moving

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Reciprocal Regulation of Brain and Muscle Arnt-Like Protein 1 and Peroxisome Proliferator-Activated Receptor α Defines a Novel Positive Feedback Loop in the Rodent Liver Circadian Clock

Molecular Endocrinology ◽

10.1210/me.2006-0052 ◽

2006 ◽

Vol 20 (8) ◽

pp. 1715-1727 ◽

Cited By ~ 224

Author(s):

Laurence Canaple ◽

Juliette Rambaud ◽

Ouria Dkhissi-Benyahya ◽

Béatrice Rayet ◽

Nguan Soon Tan ◽

...

Keyword(s):

Gene Expression ◽

Circadian Rhythm ◽

Feedback Loop ◽

Clock Gene ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Reciprocal Regulation ◽

Clock Gene Expression ◽

Regulatory Feedback Loop

Abstract Recent evidence has emerged that peroxisome proliferator-activated receptor α (PPARα), which is largely involved in lipid metabolism, can play an important role in connecting circadian biology and metabolism. In the present study, we investigated the mechanisms by which PPARα influences the pacemakers acting in the central clock located in the suprachiasmatic nucleus and in the peripheral oscillator of the liver. We demonstrate that PPARα plays a specific role in the peripheral circadian control because it is required to maintain the circadian rhythm of the master clock gene brain and muscle Arnt-like protein 1 (bmal1) in vivo. This regulation occurs via a direct binding of PPARα on a potential PPARα response element located in the bmal1 promoter. Reversely, BMAL1 is an upstream regulator of PPARα gene expression. We further demonstrate that fenofibrate induces circadian rhythm of clock gene expression in cell culture and up-regulates hepatic bmal1 in vivo. Together, these results provide evidence for an additional regulatory feedback loop involving BMAL1 and PPARα in peripheral clocks.

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Acute Knockdown of Kv4.1 Regulates Repetitive Firing Rates and Clock Gene Expression in the Suprachiasmatic Nucleus and Daily Rhythms in Locomotor Behavior

eNeuro ◽

10.1523/eneuro.0377-16.2017 ◽

2017 ◽

Vol 4 (3) ◽

pp. ENEURO.0377-16.2017 ◽

Cited By ~ 11

Author(s):

Tracey O. Hermanstyne ◽

Daniel Granados-Fuentes ◽

Rebecca L. Mellor ◽

Erik D. Herzog ◽

Jeanne M. Nerbonne

Keyword(s):

Gene Expression ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Locomotor Behavior ◽

Repetitive Firing ◽

Daily Rhythms ◽

Firing Rates ◽

Clock Gene Expression

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In Vivo Monitoring of Circadian Clock Gene Expression in the Mouse Suprachiasmatic Nucleus Using Fluorescence Reporters

Journal of Visualized Experiments ◽

10.3791/56765 ◽

2018 ◽

Author(s):

Long Mei ◽

Cheng Zhan ◽

Eric Erquan Zhang

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Circadian Clock Gene ◽

Clock Gene Expression

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Daily rhythms in clock gene expression in the mouse pineal gland

10.1240/sav_gbm_2003_m_000370 ◽

2003 ◽

Vol 2003 (Spring) ◽

Author(s):

Magdalena Karolczak ◽

Guido J. Burbach ◽

Horst-Werner Korf ◽

Jörg H. Stehle

Keyword(s):

Gene Expression ◽

Pineal Gland ◽

Clock Gene ◽

Daily Rhythms ◽

Clock Gene Expression

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Altered energy intake and the amplitude of the body temperature rhythm are associated with changes in phase, but not amplitude, of clock gene expression in the rat suprachiasmatic nucleus in vivo

Chronobiology International ◽

10.3109/07420528.2015.1112395 ◽

2016 ◽

Vol 33 (1) ◽

pp. 85-97 ◽

Cited By ~ 8

Author(s):

Grace H. Goh ◽

Peter J. Mark ◽

Shane K. Maloney

Keyword(s):

Gene Expression ◽

Body Temperature ◽

Energy Intake ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

The Body ◽

Clock Gene Expression ◽

Temperature Rhythm ◽

Body Temperature Rhythm

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Daily rhythms of clock gene expression, glycaemia and digestive physiology in diurnal/nocturnal European seabass

Physiology & Behavior ◽

10.1016/j.physbeh.2012.03.006 ◽

2012 ◽

Vol 106 (4) ◽

pp. 446-450 ◽

Cited By ~ 20

Author(s):

Ana del Pozo ◽

Ander Montoya ◽

Luisa María Vera ◽

Francisco Javier Sánchez-Vázquez

Keyword(s):

Gene Expression ◽

Clock Gene ◽

Digestive Physiology ◽

Daily Rhythms ◽

Clock Gene Expression ◽

European Seabass

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Altered clock gene expression and vascular smooth muscle diurnal contractile variations in type 2 diabetic db/db mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00825.2011 ◽

2012 ◽

Vol 302 (3) ◽

pp. H621-H633 ◽

Cited By ~ 43

Author(s):

Wen Su ◽

Zhongwen Xie ◽

Zhenheng Guo ◽

Marilyn J. Duncan ◽

Jenny Lutshumba ◽

...

Keyword(s):

Smooth Muscle ◽

Clock Gene ◽

Mesenteric Arteries ◽

Mrna Levels ◽

Clock Gene Expression ◽

Pressor Responses ◽

Related Proteins ◽

Type 2 Diabetic

This study was designed to determine whether the 24-h rhythms of clock gene expression and vascular smooth muscle (VSM) contractile responses are altered in type 2 diabetic db/db mice. Control and db/db mice were euthanized at 6-h intervals throughout the day. The aorta, mesenteric arteries, heart, kidney, and brain were isolated. Clock and target gene mRNA levels were determined by either real-time PCR or in situ hybridization. Isometric contractions were measured in isolated aortic helical strips, and pressor responses to an intravenous injection of vasoconstrictors were determined in vivo using radiotelemetry. We found that the 24-h mRNA rhythms of the following genes were suppressed in db/db mice compared with control mice: the clock genes period homolog 1/2 ( Per1/2) and cryptochrome 1/2 ( Cry1/2) and their target genes D site albumin promoter-binding protein ( Dbp) and peroxisome proliferator-activated receptor-γ ( Pparg) in the aorta and mesenteric arteries; Dbp in the heart; Per1, nuclear receptor subfamily 1, group D, member 1 ( Rev-erba), and Dbp in the kidney; and Per1 in the suprachiasmatic nucleus. The 24-h contractile variations in response to phenylephrine (α1-agonist), ANG II, and high K+ were significantly altered in the aortas from db/db mice compared with control mice. The diurnal variations of the in vivo pressor responses to phenylephrine and ANG II were lost in db/db mice. Moreover, the 24-h mRNA rhythms of the contraction-related proteins Rho kinase 1/2, PKC-potentiated phosphatase inhibitory protein of 17 kDa, calponin-3, tropomyosin-1/2, and smooth muscle protein 22-α were suppressed in db/db mice compared with control mice. Together, our data demonstrated that the 24-h rhythms of clock gene mRNA, mRNA levels of several contraction-related proteins, and VSM contraction were disrupted in db/db mice, which may contribute to the disruption of their blood pressure circadian rhythm.

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