Network Dynamics Mediate Circadian Clock Plasticity

Azzi, Abdelhalim; Evans, Jennifer; Leise, Tanya; Myung, Jihwan; Takumi, Toru; Davidson, Alec J.; Brown, Steven A.

doi:10.1016/j.neuron.2016.12.022

Cited by 73 publications

(96 citation statements)

References 58 publications

(89 reference statements)

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“…In Azzi et al . (), the intrinsic dorsal SCN period of PER2::LUC oscillation does not change significantly after entrainment under 22‐h and 26‐h days.…”

Section: Translating Physiological Heterogeneity In the Scn Into Modementioning

confidence: 82%

“…The fact that there is a seasonal change in the chloride transporter expression at the transcriptional‐level implies that the coupling parameter K is given through epigenetic modifications (Myung et al ., ). In T‐cycle experiments, it has been directly demonstrated that the long‐term change in circadian rhythms is due to DNA methylation (Azzi et al ., , ).…”

Section: Discussionmentioning

confidence: 99%

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Encoding seasonal information in a two‐oscillator model of the multi‐oscillator circadian clock

Myung

Pauls

2017

Eur J of Neuroscience

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The suprachiasmatic nucleus (SCN) is a collection of about 10 000 neurons, each of which functions as a circadian clock with slightly different periods and phases, that work in concert with form and maintain the master circadian clock for the organism. The diversity among neurons confers on the SCN the ability to robustly encode both the 24-h light pattern as well as the seasonal time. Cluster synchronization brings the different neurons into line and reduces the large population to essentially two oscillators, coordinated by a macroscopic network motif of asymmetric repulsive-attractive coupling. We recount the steps leading to this simplification and rigorously examine the two-oscillator case by seeking an analytical solution. Through these steps, we identify physiologically relevant parameters that shape the behaviour of the SCN network and delineate its ability to store past details of seasonal variation in photoperiod.

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“…In Azzi et al . (), the intrinsic dorsal SCN period of PER2::LUC oscillation does not change significantly after entrainment under 22‐h and 26‐h days.…”

Section: Translating Physiological Heterogeneity In the Scn Into Modementioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Encoding seasonal information in a two‐oscillator model of the multi‐oscillator circadian clock

Myung

Pauls

2017

Eur J of Neuroscience

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“…As stem cells differentiate, cell junctions and direct communication between cells typically increase, e.g., through increased E‐cadherin versus N‐cadherin expression. Evidence indicates that changes in cell‐cell communication occur rhythmically in the SCN (Prosser et al, 2003) and also alter the circadian period, which could represent an adaptive neural plasticity along with chemical synapse modifications (Azzi et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Musashi‐2 and related stem cell proteins in the mouse suprachiasmatic nucleus and their potential role in circadian rhythms

Beligala

Malik

et al. 2019

Intl J of Devlp Neuroscience

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Background The suprachiasmatic nucleus (SCN) of the mammalian hypothalamus contains the master circadian clock of the body and an unusually large number of cells expressing stem cell‐related proteins. These seemingly undifferentiated cells may serve in entrainment of the SCN circadian clock to light cycles or allow it to undergo neural plasticity important for modifying its rhythmic output signals. These cells may also proliferate and differentiate into neurons or glia in response to episodic stimuli or developmental events requiring alterations in the SCN's control of physiology and behavior. Problem To characterize expression of stem cell related proteins in the SCN and the effects of stem‐like cells on circadian rhythms. Methods Explant cultures of mouse SCN were maintained in medium designed to promote survival and growth of stem cells but not neuronal cells. Several stem cell marker proteins including SRY‐box containing gene 2 (SOX2), nestin, vimentin, octamer‐binding protein 4 (OCT4), and Musashi RNA‐binding protein 2 (MSI2) were identified by immunocytochemistry in histological sections from adult mouse SCN and in cultures of microdissected SCN. A bioinformatics analysis located potential SCN targets of MSI2 and related RNA‐binding proteins. Results Cells expressing stem cell markers proliferated in culture. Immunostained brain sections and bioinformatics supported the view that MSI2 regulates immature properties of SCN neurons, potentially providing flexibility in SCN neural circuits. Explant cultures had ongoing mitotic activity, indicated by proliferating‐cell nuclear antigen, and extensive cell loss shown by propidium iodide staining. Cells positive for vasoactive intestinal polypeptide (VIP) that are highly enriched in the SCN were diminished in explant cultures. Despite neuronal cell loss, tissue remained viable for over 7 weeks in culture, as shown by bioluminescence imaging of explants prepared from SCN of Per1::luc transgenic mice. The circadian rhythm in SCN gene expression persisted in brain slice cultures in stem cell medium. Prominent, widespread expression of RNA‐binding protein MSI2 supported the importance of posttranscriptional regulation in SCN functions and provided further evidence of stem‐like cells. Conclusion The results show that the SCN retains properties of immature neurons and these properties persist in culture conditions suitable for stem cells, where the SCN stem‐like cells also proliferate. These properties may allow adaptive circadian rhythm adjustments. Further exploration should examine stem‐like cells of the SCN in vivo, how they may affect circadian rhythms, and whether MSI2 serves as a master regulator of SCN stem‐like properties.

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“…The mHypoE N36/1 neuronal line was selected as these cells provide an optimal in vitro model to complement the hypothalamic oestrous analyses conducted in Study 1. Furthermore, because de novo DNA methyltransferase enzymes are expressed across multiple hypothalamic nuclei; these cells provide a model to identify the effect of DES and hyper‐ and hypo‐DNA methylation agents on select neuroendocrine targets. Cells were grown in a humidified incubator at 37°C in 5% CO 2 in Dulbecco's modified Eagle’s medium (high glucose; 4500 mg L ‐1 glucose, l ‐glutamine and sodium bicarbonate (D5796; Sigma‐Aldrich), supplemented with fetal bovine serum (10%; American Type Culture Collection, Manassas, VA, USA), penicillin (10 units mL ‐1 ) and streptomycin (10 µg mL ‐1 ) (Pen/Strep 100X; Thermo Fisher Scientific) in T75 flasks (Fisher Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Ovarian hormones induce de novo DNA methyltransferase expression in the Siberian hamster suprachiasmatic nucleus

Coyle

Caso

Tolla

et al. 2020

J Neuroendocrinology

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The present study investigated neuroanatomically localised changes in de novo DNA methyltransferase expression in the female Siberian hamster (Phodopus sungorus). The objectives were to identify the neuroendocrine substrates that exhibit rhythmic Dnmt3a and Dnmt3b expression across the oestrous cycle and also examine the role of ovarian steroids. Hypothalamic Dnmt3a expression was observed to significantly increase during the transition from pro‐oestrous to oestrous. A single bolus injection of diethylstilbestrol and progesterone was sufficient to increase Dnmt3a cell numbers and Dnmt3b immunoreactive intensity in the suprachiasmatic nucleus. In vitro analyses using an embryonic rodent cell line revealed that diethylstilbestrol was sufficient to induce Dnmt3b expression. Up‐regulating DNA methylation in vitro reduced the expression of vasoactive intestinal polypeptide, Vip, and the circadian clock gene, Bmal1. Together, these data indicate that ovarian steroids drive de novo DNA methyltransferase expression in the mammalian suprachiasmatic nucleus and increased methylation may regulate genes involved in the circadian timing of oestrous: Vip and Bmal1. Overall, epigenetically mediated neuroendocrine reproductive events may reflect an evolutionarily ancient process involved in the timing of female fertility.

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Network Dynamics Mediate Circadian Clock Plasticity

Cited by 73 publications

References 58 publications

Encoding seasonal information in a two‐oscillator model of the multi‐oscillator circadian clock

Encoding seasonal information in a two‐oscillator model of the multi‐oscillator circadian clock

Musashi‐2 and related stem cell proteins in the mouse suprachiasmatic nucleus and their potential role in circadian rhythms

Ovarian hormones induce de novo DNA methyltransferase expression in the Siberian hamster suprachiasmatic nucleus

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