Resetting the Biological Clock: Mediation of Nocturnal CREB Phosphorylation via Light, Glutamate, and Nitric Oxide

Ding, Jian; Faiman, Lia E.; Hurst, William J.; Kuriashkina, Liana; Gillette, Martha U.

doi:10.1523/jneurosci.17-02-00667.1997

Cited by 225 publications

(169 citation statements)

References 80 publications

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“…Glutamate (1mM) applied for 10 min at ZT 23 induced robust phase advances of about 3 h (Fig. 5), consistent with previously reported results in rats (Ding et al, 1994;Ding et al, 1997;Ding et al, 1998). As seen with glutamate-induced phase delays, co-application of 20 mM ethanol completely blocked glutamate-induced phase advances, while having no effect on the phase of neuronal activity when applied alone.…”

Section: Ethanol Inhibition Of Glutamate-induced Phase Advances Is Insupporting

confidence: 91%

“…Previous work has shown that glutamate-induced phase shifts require generation of nitric oxide (NO) (Ding et al, 1994;Ding et al, 1997), and in vitro application of glutamate to SCN slices induces NO production that is inhibited by AP5, K252a and the nitric oxide synthase (NOS) antagonist, L-NAME (R.A. Prosser and Y. Lee, unpublished results). Here we tested whether DPAT-induced phase shifts are enhanced by blocking NOS activity with L-NAME.…”

Section: Blocking Nitric Oxide Generation Enhances Serotonergic Phasementioning

confidence: 99%

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Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro

2008

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Alcohol abuse is associated with sleep problems, which are often linked to circadian rhythm disturbances. However, there is no information on the direct effects of ethanol on the mammalian circadian clock. Acute ethanol inhibits glutamate signaling, which is the primary mechanism through which light resets the mammalian clock in the suprachiasmatic nucleus (SCN). Glutamate and light also inhibit circadian clock resetting induced by non-photic signals, including serotonin. Thus, we investigated the effects of acute ethanol on both glutamatergic and serotoninergic resetting of the SCN clock in vitro. We show that ethanol dose-dependently inhibits glutamate-induced phase shifts and enhances serotonergic phase shifts. The inhibition of glutamate-induced phase shifts is not affected by excess glutamate, glycine or D-serine, but is prevented by excess brain-derived neurotrophic factor (BDNF). BDNF is known to augment glutamate signaling in the SCN and to be necessary for glutamate/light-induced phase shifts. Thus, ethanol may inhibit glutamate-induced clock resetting at least in part by blocking BDNF enhancement of glutamate signaling. Ethanol enhancement of serotonergic phase shifts is mimicked by treatments that suppress glutamate signaling in the SCN, including antagonists of glutamate receptors, BDNF signaling and nitric oxide synthase. The combined effect of ethanol with these treatments is not additive, suggesting they act through a common pathway. Our data indicate further that the interaction between serotonin and glutamate in the SCN may occur downstream from nitric oxide synthase activation. Thus, acute ethanol disrupts normal circadian clock phase regulation, which could contribute to the physiological and psychological problems associated with alcohol abuse. Keywords suprachiasmatic nucleus; circadian rhythms; ethanol; glutamate; serotonin; brain-derived neurotrophic factorThe development of alcoholism and the likelihood of relapse drinking are associated with poor sleep quality and the deleterious effects of ethanol on sleep (Landolt and Gillin, 2001;Brower et al., 2001). Alcohol consumption reduces sleep quality (Kubota et al., 2002;Ehler and Slawecki, 2000;Landolt et al., 1996), which is closely linked to the circadian system. For example, the inability to fall asleep at the desired time can result from improper synchronization *Corresponding author: Dept. Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, phone: (865) 974-2722, FAX: (865)-974-6306, rprosser@utk.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal per...

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Section: Ethanol Inhibition Of Glutamate-induced Phase Advances Is Insupporting

confidence: 91%

Section: Blocking Nitric Oxide Generation Enhances Serotonergic Phasementioning

confidence: 99%

Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro

2008

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“…[20][21][22][23] Alterations in sGC expression and function in the brain in cirrhotic patients, therefore, could relate to the neuropsychiatric symptoms such as sleep disturbances and memory …”

Section: Discussionmentioning

confidence: 99%

Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients

et al. 2002

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Modulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) is altered in brain from experimental animals with hyperammonemia with or without liver failure. The aim of this work was to assess the content and modulation of sGC in brain in chronic liver failure in humans. Expression of the ␣-1, ␣-2, and ␤-1 subunits of sGC was measured by immunoblotting in autopsied frontal cortex and cerebellum from cirrhotic patients and controls. The contents of ␣-1 and ␣-2 subunits of guanylate cyclase was increased both in cortex and cerebellum, whereas the ␤-1 subunit was not affected. Addition of the NO-generating agent S-nitroso-N-acetyl-penicillamine (SNAP) to homogenates of frontal cortex from controls increased the activity of sGC 87-fold, whereas, in homogenates from cirrhotic patients, the increase was significantly higher (183-fold). In contrast, in cerebellum, activation of guanylate cyclase by NO was significantly lower in patients (156-fold) than in controls (248-fold). A similar regional difference was found in rats with portacaval anastomosis. In conclusion, these findings show that the NO-guanylate cyclase signal transduction pathway is strongly altered in brain in patients with chronic liver failure and that the effects are different in different brain areas. Given that activation of sGC by NO in brain is involved in the modulation of important cerebral processes such as intercellular communication, learning and memory, and the sleep-wake cycle, these changes could be implicated in the pathogenesis of hepatic encephalopathy in these patients. (HEPATOLOGY 2002;36:1155-1162 T he pathophysiologic mechanisms responsible for hepatic encephalopathy (HE) in chronic liver failure are incompletely understood. However, disruption of neurotransmitter systems has increasingly been implicated. In particular, selective alterations of glutamatergic and monoaminergic receptor sites have been reported in both experimental animal models of HE 1,2 and the brains of human cirrhotic patients. 3,4 Many of these receptors are functionally coupled to the nitric oxide (NO) cyclic guanosine monophosphate (cGMP) signal transduction pathway, which serves to amplify the postsynaptic response to receptor activation.Previous studies provide evidence for a role for this signal transduction pathway in the mediation of important cerebral functions, including regulation of the sleepwake cycle and some components of learning and memory, abnormalities of which form part of the spectrum of neuropsychiatric symptoms, which characterize HE in chronic liver failure. Furthermore, recent studies in experimental chronic liver failure reveal significant alterations in expression of key components of this signal transduction pathway. Such evidence includes increased expression and activities of neuronal nitric oxide synthase (nNOS) 5 and of the ␣ subunit of soluble guanylate cyclase (sGC). 6 The purpose of the present study was, therefore, to evaluate the NO-cGMP signal transduction pathway in relation to human HE. To accomplish this, the content o...

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“…Light administered in the dark phase is thought to elicit glutamate release in the synapses of the RHT, because glutamate can mimic the effects of light. Glutamate activates ionotropic glutamate receptors in the SCN, which trigger influx of Ca 2+ (Ding et al, 1994(Ding et al, , 1997Schurov et al, 1999). This leads to the activation of several signal transduction pathways (reviewed in Hirota & Fukada, 2004) and evokes modification of chromatin (Crosio et al, 2000) and clock proteins (Myers et al, 1996) plus the activation of immediate early genes, such as c-Fos (Kornhauser et al, 1990) and the clock genes Per1 and Per2 (Albrecht et al, 1997;Shearman et al, 1997;Shigeyoshi et al 1997;Yan & Silver, 2002).…”

Section: Introductionmentioning

confidence: 99%

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Stadler

Schmutz

Schwaller

et al. 2010

Chronobiology International

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A strong stimulus adjusting the circadian clock to the prevailing light-dark cycle is light. However, the circadian clock is reset by light only at specific times of the day. The mechanisms mediating such gating of light input to the CNS are not well understood. There is evidence that Ca 2+ ions play an important role in intracellular signaling mechanisms, including signaling cascades stimulated by light. Therefore, Ca 2+ is hypothesized to play a role in the light-mediated resetting of the circadian clock. Calbindin-D28k (CB; gene symbol: Calb1) is a Ca 2+ binding protein implicated in Ca 2+ homeostasis and sensing. The absence of this protein influences Ca 2+ buffering capacity of a cell, alters spatio-temporal aspects of intracellular Ca 2+ signaling, and hence might alter transmission of light information to the circadian clock in neurons of the suprachiasmatic nuclei (SCN). We tested mice lacking a functional Calb1 gene (Calb1 −/−) and found an increased phase-delay response to light applied at circadian time (CT) 14 in these animals. This is accompanied by elevated induction of Per2 gene expression in the SCN. Period length and circadian rhythmicity were comparable between Calb1 −/− and wild-type animals. Our findings indicate an involvement of CB in the signaling pathway that modulates the behavioral and molecular response to light.

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Resetting the Biological Clock: Mediation of Nocturnal CREB Phosphorylation via Light, Glutamate, and Nitric Oxide

Cited by 225 publications

References 80 publications

Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro

Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro

Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

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