Copper chelation and exogenous copper affect circadian clock phase resetting in the suprachiasmatic nucleus in vitro

Neuroscience ◽  
2014 ◽  
Vol 256 ◽  
pp. 252-261 ◽  
Author(s):  
Y. Yamada ◽  
R.A. Prosser
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Phase Resetting ◽  
Copper Chelation

The Mammalian Circadian Clock in the Suprachiasmatic Nucleus Exhibits Rapid Tolerance to Ethanol In Vivo and In Vitro

2014 ◽  
Vol 38 (3) ◽  
pp. 760-769 ◽  
Author(s):  
Jonathan H. Lindsay ◽  
J. David Glass ◽  
Mario Amicarelli ◽  
Rebecca A. Prosser
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Tolerance To Ethanol

scholarly journals Activation of AMPA Receptors in the Suprachiasmatic Nucleus Phase-Shifts the Mouse Circadian Clock In Vivo and In Vitro

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10951 ◽  
Author(s):  
Yasutaka Mizoro ◽  
Yoshiaki Yamaguchi ◽  
Rena Kitazawa ◽  
Hiroyuki Yamada ◽  
Masahiro Matsuo ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Ampa Receptors ◽  
Phase Shifts

scholarly journals Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster

2009 ◽  
Vol 296 (2) ◽  
pp. R411-R418 ◽  
Author(s):  
Christina L. Ruby ◽  
Rebecca A. Prosser ◽  
Marc A. DePaul ◽  
Randy J. Roberts ◽  
J. David Glass
Keyword(s):  
Circadian Clock ◽  
Activity Rhythm ◽  
Direct Action ◽  
Glutamate Release ◽  
Extracellular Fluid ◽  
Circadian Rhythmicity ◽  
Phase Resetting ◽  
Circadian Phase ◽  
Acute Ethanol

Disrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT1A,7 agonist, 8-OH-DPAT. To explore the basis of these effects in the whole animal, we used microdialysis to characterize the pharmacokinetics of intraperitoneal injection of EtOH in the hamster SCN extracellular fluid compartment and then studied the effects of such EtOH treatment on photic and serotonergic phase resetting of the circadian locomotor activity rhythm. Peak EtOH levels (∼50 mM) from a 2 g/kg injection occurred within 20–40 min with a half-life of ∼3 h. EtOH treatment dose-dependently attenuated photic phase advances but had no effect on phase delays and, contrary to in vitro findings, markedly attenuated 8-OH-DPAT-induced phase advances. In a complementary experiment using reverse microdialysis to deliver a timed SCN perfusion of EtOH during a phase-advancing light pulse, the phase advances were blocked, similar to systemic EtOH treatment. These results are evidence that acute EtOH significantly affects photic and nonphotic phase-resetting responses critical to circadian clock regulation. Notably, EtOH inhibition of photic signaling is manifest through direct action in the SCN. Such actions could underlie the disruption of circadian rhythmicity associated with alcohol abuse.

scholarly journals Circadian clock control of eIF2α phosphorylation is necessary for rhythmic translation initiation

2020 ◽  
Vol 117 (20) ◽  
pp. 10935-10945 ◽  
Author(s):  
Shanta Karki ◽  
Kathrina Castillo ◽  
Zhaolan Ding ◽  
Olivia Kerr ◽  
Teresa M. Lamb ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Nutrient Metabolism ◽  
Eif2α Phosphorylation ◽  
Eif2α Kinase ◽  
The Impact

The circadian clock in eukaryotes controls transcriptional and posttranscriptional events, including regulation of the levels and phosphorylation state of translation factors. However, the mechanisms underlying clock control of translation initiation, and the impact of this potential regulation on rhythmic protein synthesis, were not known. We show that inhibitory phosphorylation of eIF2α (P-eIF2α), a conserved translation initiation factor, is clock controlled in Neurospora crassa, peaking during the subjective day. Cycling P-eIF2α levels required rhythmic activation of the eIF2α kinase CPC-3 (the homolog of yeast and mammalian GCN2), and rhythmic activation of CPC-3 was abolished under conditions in which the levels of charged tRNAs were altered. Clock-controlled accumulation of P-eIF2α led to reduced translation during the day in vitro and was necessary for the rhythmic synthesis of select proteins in vivo. Finally, loss of rhythmic P-eIF2α levels led to reduced linear growth rates, supporting the idea that partitioning translation to specific times of day provides a growth advantage to the organism. Together, these results reveal a fundamental mechanism by which the clock regulates rhythmic protein production, and provide key insights into how rhythmic translation, cellular energy, stress, and nutrient metabolism are linked through the levels of charged versus uncharged tRNAs.

Ras Activity Oscillates in the Mouse Suprachiasmatic Nucleus and Modulates Circadian Clock Dynamics

2015 ◽  
Vol 53 (3) ◽  
pp. 1843-1855 ◽  
Author(s):  
Tsvetan Serchov ◽  
Antje Jilg ◽  
Christian T. Wolf ◽  
Ina Radtke ◽  
Jörg H. Stehle ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus

Neuropeptide Y and glutamate block each other's phase shifts in the suprachiasmatic nucleus in vitro

Neuroscience ◽  
1997 ◽  
Vol 77 (4) ◽  
pp. 1049-1057 ◽  
Author(s):  
S.M Biello ◽  
D.A Golombek ◽  
M.E Harrington
Keyword(s):  
Neuropeptide Y ◽  
Suprachiasmatic Nucleus ◽  
Phase Shifts

scholarly journals GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the suprachiasmatic nucleus neurons

2017 ◽  
Vol 118 (6) ◽  
pp. 3092-3106 ◽  
Author(s):  
Michael Moldavan ◽  
Olga Cravetchi ◽  
Charles N. Allen
Keyword(s):  
Circadian Clock ◽  
Suprachiasmatic Nucleus ◽  
Dependent Manner ◽  
Circadian Period ◽  
Gaba Concentration ◽  
Gaba Transporter ◽  
Concentration Dependent Manner ◽  
Gaba Transport ◽  
Gaba Transporters ◽  
Tonic Current

GABA is a principal neurotransmitter in the hypothalamic suprachiasmatic nucleus (SCN) that contributes to intercellular communication between individual circadian oscillators within the SCN network and the stability and precision of the circadian rhythms. GABA transporters (GAT) regulate the extracellular GABA concentration and modulate GABAA receptor (GABAAR)-mediated currents. GABA transport inhibitors were applied to study how GABAAR-mediated currents depend on the expression and function of GAT. Nipecotic acid inhibits GABA transport and induced an inward tonic current in concentration-dependent manner during whole cell patch-clamp recordings from SCN neurons. Application of either the selective GABA transporter 1 (GAT1) inhibitors NNC-711 or SKF-89976A, or the GABA transporter 3 (GAT3) inhibitor SNAP-5114, produced only small changes of the baseline current. Coapplication of GAT1 and GAT3 inhibitors induced a significant GABAAR-mediated tonic current that was blocked by gabazine. GAT inhibitors decreased the amplitude and decay time constant and increased the rise time of spontaneous GABAAR-mediated postsynaptic currents. However, inhibition of GAT did not alter the expression of either GAT1 or GAT3 in the hypothalamus. Thus GAT1 and GAT3 functionally complement each other to regulate the extracellular GABA concentration and GABAAR-mediated synaptic and tonic currents in the SCN. Coapplication of SKF-89976A and SNAP-5114 (50 µM each) significantly reduced the circadian period of Per1 expression in the SCN by 1.4 h. Our studies demonstrate that GAT are important regulators of GABAAR-mediated currents and the circadian clock in the SCN. NEW & NOTEWORTHY In the suprachiasmatic nucleus (SCN), the GABA transporters GAT1 and GAT3 are expressed in astrocytes. Inhibition of these GABA transporters increased a tonic GABA current and reduced the circadian period of Per1 expression in SCN neurons. GAT1 and GAT3 showed functional cooperativity: inhibition of one GAT increased the activity but not the expression of the other. Our data demonstrate that GABA transporters are important regulators of GABAA receptor-mediated currents and the circadian clock.

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