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  • 1
    Electronic Resource
    Electronic Resource
    Gene expression View of a mouse clock gene ticking (2001)
    [s.l.] : Nature Publishing Group
    Nature 409 (2001), S. 684-684 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Circadian clocks consist of an ingenious autoregulatory feedback loop whereby the cyclically expressed products of the clock gene are able to inhibit their own expression〈. Here we follow the rhythmic expression of the clock gene mPer1 in the brain of a living mouse. This model system ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35055628
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  • 2
    Electronic Resource
    Electronic Resource
    Facilitation of α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study was designed to test whether the α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-facilitating drug, aniracetam, could potentiate photic responses of the biological clock in the suprachiasmatic nucleus (SCN) of rodents. Using the whole-cell patch technique, we first demonstrated that AMPA currents elicited by either local AMPA application or optic chiasm stimulation were augmented by aniracetam in the neurons of the SCN. The AMPA application-elicited increase of intracellular Ca2+ concentration in SCN slices was also enhanced by aniracetam treatment. The systemic injection of aniracetam dose-dependently (10–100 mg/kg) potentiated the phase delay in behavioral rhythm induced by brief light exposure of low intensity (3 lux) but not high intensity (10 or 60 lux) during early subjective night. Under the blockade of NMDA receptors by (+) MK801, aniracetam failed to potentiate a light (3 lux)-induced phase delay in behavioral rhythm. Aniracetam increased the photic induction of c-Fos protein in the SCN that was elicited by low intensity light exposure (3 lux). These results suggest that AMPA receptor-mediated responses facilitated by aniracetam can explain enhanced photic responses of the biological clock in the SCN of rodents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01758.x
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  • 3
    Electronic Resource
    Electronic Resource
    Involvement of calcium–calmodulin protein kinase but not mitogen-activated protein kinase in light-induced phase delays and Per gene expression in the suprachiasmatic nucleus of the hamster (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 77 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It is known that Ca2+-dependent phosphorylation of cAMP response element binding protein (CREB) and the rapid induction of mPer1 and mPer2, mouse period genes in the suprachiasmatic nucleus (SCN) are associated with light-induced phase shifting. The CREB/CRE transcriptional pathway has been shown to be activated by calcium/calmodulin dependent kinase II (CaMKII) and mitogen-activated protein kinase (MAPK); however, there is a lack of evidence concerning whether the activation of CaMKII and/or MAPK elicited by photic stimuli are associated with the change in Per gene expression and behavioral phase shifting. In this experiment, we found there was an inhibitory effect by KN93, CaMKII inhibitor, on hamster Per1 and Per2 expression in the SCN and on phase delays in wheel running rhythm induced by light pulses. PD98059 and U0126, MAPK kinase inhibitors, however, affected neither light-induced Per1 and Per2 expression nor behavioral phase delays, even though PD98059 attenuated the light-induced phosphorylation of MAPK in the SCN. The present findings demonstrate that the light-induced activation of CaMKII plays an important role in the induction of Per1 and Per2 mRNA in the hamster SCN as well as phase shifting. These results suggest that gated induction of Per1 and/or Per2 genes through CaMKII-CREB/CRE accompanied with photic stimuli may be a critical step in phase shifting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00270.x
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  • 4
    Electronic Resource
    Electronic Resource
    Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 78 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mammalian circadian clock genes Per1 and Per2 are rhythmically expressed not only in the suprachiasmatic nucleus where the mammalian circadian clock exists, but also in other brain regions and peripheral tissues. The induced circadian oscillation of Per genes after treatment with high concentrations of serum or various drugs in cultured cells suggests the ubiquitous existence of the oscillatory mechanism. These treatments also result in a rapid surge of expression of Per1. It has been shown that multiple signaling pathways are involved in Per1 gene induction in culture cells. We used a dispersed primary cell culture made up of mouse cerebellar granule cells to examine the stimuli inducing the mPer genes and their signaling pathways in neuronal tissues expressing mPer genes. We demonstrated that mPer1, but not mPer2, mRNA expression was dependent on the depolarization state controlled by extracellular KCl concentration in the granule cell culture. Nifedipine treatment reduced mPer1 induction, suggesting that mPer1 mRNA expression depends on intracellular calcium concentration regulated through a voltage-dependent Ca2+ channel. Transient mPer1 mRNA induction was observed after elevating KCl concentration in the medium from 5 mm to 25 mm. This increased expression was suppressed by a calmodulin antagonist, or CaMKII/IV inhibitor, but not by MEK inhibitors. Addition of pituitary adenylate cyclase-activating polypeptide-38 to the medium also induced transient Per1 gene expression. This induction was mimicked by dibutyryl-cAMP and suppressed by a protein kinase A (PKA) inhibitor, but not by MEK inhibitors. These results suggest that Ca2+/calmodulin-dependent protein kinase II/IV- and PKA-dependent pathways are involved in high-KCl and PACAP-induced mPer1 induction, respectively, and neural tissues use multiple signaling pathways for mPer1 induction similar to culture cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00452.x
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  • 5
    Electronic Resource
    Electronic Resource
    Methamphetamine-induced, suprachiasmatic nucleus-independent circadian rhythms of activity and mPer gene expression in the striatum of the mouse (2002)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 16 (2002), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: While the suprachiasmatic nucleus (SCN) coordinates the majority of daily rhythms, some circadian patterns of expression are controlled from outside of the SCN. These include responses to daily methamphetamine (MAP) injection, or daily restricted feeding. The mechanisms underlying these SCN-independent circadian rhythms are unknown. A circadian oscillation in the expression of mPer1 and/or mPer2, mouse period, in the SCN is considered necessary to generate an SCN-dependent circadian rhythm. Therefore, in this experiment, we examined the association between mPer gene expression and the MAP-induced, SCN-independent circadian rhythm. Acute injection of MAP caused an elevation of mPer1, mBmal1, and mNpas2 gene expression in the striatum and mPer1 in the liver. Daily MAP injection at a fixed time for 6 days shifted the rhythmic mPer1 and mPer2 expression in the striatum from a nocturnal to a diurnal rhythm, but failed to affect that in the SCN. Although lesion of the SCN ‘flattened’mPer gene oscillation in the striatum and liver, daily MAP injection caused both behavioural and mPer gene expression rhythms. Daily MAP injection at variable injection intervals (12–36 h) for 6 days, however, failed to produce mPer gene rhythm in the striatum. Daily repeated MAP signals may strengthen the oscillatory force of SCN-independent circadian behavioural and molecular rhythms. The present results suggest that daily oscillation of mPer genes outside the SCN is closely associated with the regulation of SCN-independent rhythms. Thus, the present experiment highlights strongly the important role of clock gene expression, in the brain, that underlies the circadian behavioural rhythm.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2002.02140.x
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  • 6
    Electronic Resource
    Electronic Resource
    Restricted-feeding-induced anticipatory activity rhythm is associated with a phase-shift of the expression of mPer1 and mPer2 mRNA in the cerebral cortex and hippocampus but not in the suprachiasmatic nucleus of mice (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Daily restricted feeding (RF) can produce food-entrainable oscillations in both intact and suprachiasmatic nucleus (SCN)-lesioned animals. Thus, there are two circadian rhythms, one of which is SCN-dependent and the other SCN-independent. Recently, it has been established that several mouse clock genes, such as mPer1, mPer2 and mPer3 are expressed in the SCN and other brain tissues. Although the role of mPer genes expressed in the SCN has recently been evaluated in the SCN-dependent rhythm, their function in the SCN-independent rhythm is still poorly understood. In order to understand the role of these genes in SCN-independent rhythm, we examined the expression pattern of mPer1 and mPer2 mRNA in each brain area of mice under RF. Mice were allowed access to food for 4 h during either the daytime under a light-dark cycle or the subjective daytime under constant dark. After 6 days of scheduled RF, the night-time or subjective night-time peak of mPer mRNA changed to a daytime peak in the cerebral cortex and hippocampus, with moderate expression in the striatum, pyriform cortex and paraventricular nucleus, and no expression in the SCN. The daytime peak in the cerebral cortex returned to a night-time peak after the release of RF to a free-feeding schedule. Although the basal rhythm of mPer expression disappeared in SCN-lesioned mice, RF produced mPer mRNA rhythm in the cerebral cortex of these mice. The present results provide evidence of an association between food-entrainable oscillations and the expression of mPer1 and mPer2 in the cerebral cortex and hippocampus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01483.x
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  • 7
    Electronic Resource
    Electronic Resource
    Close linkage between calcium/calmodulin kinase II α/β and NMDA-2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The general mechanism underlying memory and learning is an area under intense investigation and debate, yet this mechanism still remains elusive. Auditory fear conditioning (when a tone is paired with a foot shock) is a simple associative form of learning for which many mechanistic details are known. Lesions of the lateral/basolateral nuclei of the amygdala result in the selective impairment of fear conditioning, indicating that this is a key region for this type of learning. Fear conditioning induces a lasting synaptic potentiation in the lateral nuclei of the amygdala. In addition, recent results from several laboratories suggest that N-methyl- d-aspartate (NMDA) receptor activation in the amygdala is required for the acquisition and expression of cue-conditioned fear responses using several kinds of antagonists. Little is known, however, about the signal transduction pathway and molecular substrate underlying fear conditioning. Here we use NMDA receptor-deficient mice to demonstrate that calmodulin-dependent kinase II, CaMKIIβ, and CaMKIIα activation involves the NR2A subunit in the lateral/basolateral amygdala during memory retrieval following auditory fear conditioning. These results suggest that auditory fear conditioning involves a close linkage between NMDA2A receptors and the CaMKII cascade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00203.x
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  • 8
    Electronic Resource
    Electronic Resource
    Differential daily expression of Per1 and Per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 13 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It is well known that there are circadian rhythms of 2-deoxyglucose uptake and neuronal firing in the rat suprachiasmatic nucleus (SCN) during fetal and early postnatal periods. A core clock mechanism in the mouse SCN appears to involve a transcriptional feedback loop in which CLOCK and BMAL1 function as positive regulators and three mPeriod (mPer) genes play a role in negative feedback. Per genes expression occurs not only in the adult SCN but also in the fetal SCN. However, the developmental change in these genes remains unclear. In this experiment, we examined the day–night pattern of expression of Per1 and Per2 mRNA in the mouse SCN and cerebral cortex on embryonic day 17, postnatal day 3, and in young adult mice under a light–dark cycle. Daily rhythms of mRNA content were observed in mPer1 but not mPer2 in the fetal SCN. Interestingly, the expression of mPer2 in the SCN was high throughout the entire day, and a significant daily rhythm of this gene was observed on postnatal day 6. The expression pattern of SCN mPer1 in constant darkness was similar to that seen in the light–dark cycle. The present results suggest that the daily oscillation of mPer1 but not of mPer2 in the SCN in fetal and early postnatal mice may be associated with the daily rhythms of 2-deoxyglucose uptake and neuronal firing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2000.01438.x
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  • 9
    Electronic Resource
    Electronic Resource
    Reduced food anticipatory activity in genetically orexin (hypocretin) neuron-ablated mice (2004)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 20 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Daily restricted feeding (RF) produces an anticipatory locomotor activity rhythm and entrains the peripheral molecular oscillator independently of the central pacemaker located in the suprachiasmatic nucleus (SCN). As orexins (hypocretins) are neuropeptides that coordinate sleep/wake patterns and motivated behaviours, such as food seeking, we studied the involvement of orexin in the food anticipatory activity (FAA) induced by RF. Daily RF shifted the mRNA rhythm of a clock-controlled gene mDbp in the cerebral cortex and caudate putamen but not in the SCN. Under these experimental conditions, prepro-orexin mRNA and orexin A immunoreactivity in the lateral hypothalamic area (LHA) did not show daily variation. Fasting increased the number of orexin A-ir cells, while RF did not. However, RF shifted the peak of Fos expression of the orexin neurons from night to day. Genetic ablation of orexin neurons in orexin/ataxin-3 transgenic mice severely reduced the formation of FAA under RF conditions. The expression of mNpas2 mRNA, a transcription factor thought to be involved in regulation of the food entrainable oscillator as well as mPer1 and mBmal1 mRNA, was reduced in the forebrain of orexin/ataxin-3 mice. Based on these results, we suggest that activity of the orexin neuron in the LHA contributes to the promotion and maintenance of FAA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.2004.03749.x
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of lithium on the circadian rhythms of locomotor activity and glycogen synthase kinase-3 protein expression in the mouse suprachiasmatic nuclei (2004)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 19 (2004), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A circadian clock located in the suprachiasmatic nucleus (SCN) regulates the period of physiological and behavioural rhythms to approximately 24 h. Lithium can lengthen the period of circadian rhythms in most organisms although little is known about the underlying mechanism. In the present study, we examined Drosophila shaggy ortholog glycogen synthase kinase-3 (GSK-3) protein expression in the SCN after lithium treatment. When locomotor activity was assessed, we found an association between the effect of lithium and the period of circadian oscillation as well as the level of GSK-3 protein expression. The decreased expression of GSK-3 and increased expression of phosphorylated GSK-3 (pGSK-3) resulted in an antiphasic circadian rhythm between the two in the SCN of lithium-treated mice housed under both light–dark and constant dark conditions. The enzyme activity of GSK-3 in the SCN was low when the level of pGSK-3 protein was high, as examined by immunoblotting analysis. Thus, GSK-3 enzyme activity has a correlation with the expression of GSK-3 protein in the SCN. Although both GSK-3 and pGSK-3 proteins are also expressed in the arcuate nucleus, lithium did not affect their expression. Based on the association that we found between lengthened circadian period and GSK-3 protein and GSK-3 activity in the SCN, we suggest that GSK-3 plays a role in regulating the period of the mammalian circadian pacemaker.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0953-816X.2004.03322.x
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