The effect of 3,4-methylenedioxymethamphetamine (‘Ecstasy’) on serotonergic regulation of the mammalian circadian clock mechanism in rats: the role of dopamine and hyperthermia

The clock mechanism for circatidal rhythm has long been controversial, and its molecular basis is completely unknown. The mangrove cricket, Apteronemobius asahinai , shows two rhythms simultaneously in its locomotor activity: a circatidal rhythm producing active and inactive phases as well as a circadian rhythm modifying the activity intensity of circatidal active phases. The role of the clock gene period ( per ), one of the key components of the circadian clock in insects, was investigated in the circadian and circatidal rhythms of A. asahinai using RNAi. After injection of double-stranded RNA of per , most crickets did not show the circadian modulation of activity but the circatidal rhythm persisted without a significant difference in the period from controls. Thus, per is functionally involved in the circadian rhythm but plays no role, or a less important role, in the circatidal rhythm. We conclude that the circatidal rhythm in A. asahinai is controlled by a circatidal clock whose molecular mechanism is different from that of the circadian clock.

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On the nature of the circadian clock in mammals

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.5.r821 ◽

1993 ◽

Vol 264 (5) ◽

pp. R821-R832 ◽

Cited By ~ 3

Author(s):

J. D. Miller

Keyword(s):

Cell Culture ◽

Functional Analysis ◽

Circadian Clock ◽

Suprachiasmatic Nucleus ◽

Response Curve ◽

Essential Role ◽

Phase Response Curve ◽

Coupling Model ◽

Clock Mechanism

The evidence for the essential role of the suprachiasmatic nucleus (SCN) for the generation and maintenance of circadian rhythms in mammals is briefly reviewed. The pharmacology of the phase-response curve is considered and a new circadian measure, the phase-dose-response surface (PDRS), is introduced. The role of neurotransmission, ion fluxes, and non-neuronal cellular elements in the generation and maintenance of circadian rhythmicity is considered. Cell culture of the SCN is proposed as a tool for the functional analysis of clock mechanism. The critical contribution of coupling and synchronization of clock elements is reviewed in the context of the explicit predictions generated by a strong coupling model of the circadian clock. Finally, the nature of the circadian output signal is analyzed from a phylogenetic viewpoint.

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Circadian Clock Genes and the Transcriptional Architecture of the Clock Mechanism

Endocrine Abstracts ◽

10.1530/endoabs.59.pl4 ◽

2018 ◽

Cited By ~ 1

Author(s):

Joseph Takahashi

Keyword(s):

Circadian Clock ◽

Clock Genes ◽

Circadian Clock Genes ◽

Clock Mechanism

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The role of the circadian clock in photoperiodism of the bean bugRiptortus pedestris

10.1603/ice.2016.91465 ◽

2016 ◽

Author(s):

Shin G. Goto

Keyword(s):

Circadian Clock

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Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation

International Journal of Molecular Sciences ◽

10.3390/ijms22073787 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3787

Author(s):

Hussam Ibrahim ◽

Philipp Reus ◽

Anna Katharina Mundorf ◽

Anna-Lena Grothoff ◽

Valerie Rudenko ◽

...

Keyword(s):

Circadian Clock ◽

Transcriptional Repression ◽

Small Gtpase ◽

Main Role ◽

Interacting Proteins ◽

Casein Kinase 1 ◽

Bona Fide ◽

Kinetics Of

Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock.

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Beyond Arabidopsis: BBX Regulators in Crop Plants

International Journal of Molecular Sciences ◽

10.3390/ijms22062906 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2906

Author(s):

Urszula Talar ◽

Agnieszka Kiełbowicz-Matuk

Keyword(s):

Stress Tolerance ◽

Crop Plants ◽

Abiotic Stress Response ◽

Biotic And Abiotic Stress ◽

Photoperiodic Regulation ◽

Large Families ◽

Stress Related Genes ◽

Unique Domain ◽

Clock Mechanism

B-box proteins represent diverse zinc finger transcription factors and regulators forming large families in various plants. A unique domain structure defines them—besides the highly conserved B-box domains, some B-box (BBX) proteins also possess CCT domain and VP motif. Based on the presence of these specific domains, they are mostly classified into five structural groups. The particular members widely differ in structure and fulfill distinct functions in regulating plant growth and development, including seedling photomorphogenesis, the anthocyanins biosynthesis, photoperiodic regulation of flowering, and hormonal pathways. Several BBX proteins are additionally involved in biotic and abiotic stress response. Overexpression of some BBX genes stimulates various stress-related genes and enhanced tolerance to different stresses. Moreover, there is evidence of interplay between B-box and the circadian clock mechanism. This review highlights the role of BBX proteins as a part of a broad regulatory network in crop plants, considering their participation in development, physiology, defense, and environmental constraints. A description is also provided of how various BBX regulators involved in stress tolerance were applied in genetic engineering to obtain stress tolerance in transgenic crops.

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Circadian clock protein Rev-erbα regulates neuroinflammation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1812405116 ◽

2019 ◽

Vol 116 (11) ◽

pp. 5102-5107 ◽

Cited By ~ 36

Author(s):

Percy Griffin ◽

Julie M. Dimitry ◽

Patrick W. Sheehan ◽

Brian V. Lananna ◽

Chun Guo ◽

...

Keyword(s):

Circadian Clock ◽

Microglial Activation ◽

Time Of Day ◽

Resting State Functional Connectivity ◽

Promoter Regions ◽

Clock Component ◽

Glial Cultures ◽

Inflammatory Phenotype

Circadian dysfunction is a common attribute of many neurodegenerative diseases, most of which are associated with neuroinflammation. Circadian rhythm dysfunction has been associated with inflammation in the periphery, but the role of the core clock in neuroinflammation remains poorly understood. Here we demonstrate that Rev-erbα, a nuclear receptor and circadian clock component, is a mediator of microglial activation and neuroinflammation. We observed time-of-day oscillation in microglial immunoreactivity in the hippocampus, which was disrupted in Rev-erbα−/− mice. Rev-erbα deletion caused spontaneous microglial activation in the hippocampus and increased expression of proinflammatory transcripts, as well as secondary astrogliosis. Transcriptomic analysis of hippocampus from Rev-erbα−/− mice revealed a predominant inflammatory phenotype and suggested dysregulated NF-κB signaling. Primary Rev-erbα−/− microglia exhibited proinflammatory phenotypes and increased basal NF-κB activation. Chromatin immunoprecipitation revealed that Rev-erbα physically interacts with the promoter regions of several NF-κB–related genes in primary microglia. Loss of Rev-erbα in primary astrocytes had no effect on basal activation but did potentiate the inflammatory response to lipopolysaccharide (LPS). In vivo, Rev-erbα−/− mice exhibited enhanced hippocampal neuroinflammatory responses to peripheral LPS injection, while pharmacologic activation of Rev-erbs with the small molecule agonist SR9009 suppressed LPS-induced hippocampal neuroinflammation. Rev-erbα deletion influenced neuronal health, as conditioned media from Rev-erbα–deficient primary glial cultures exacerbated oxidative damage in cultured neurons. Rev-erbα−/− mice also exhibited significantly altered cortical resting-state functional connectivity, similar to that observed in neurodegenerative models. Our results reveal Rev-erbα as a pharmacologically accessible link between the circadian clock and neuroinflammation.

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