Nonphotic Entrainment by 5-HT1A/7Receptor Agonists Accompanied by ReducedPer1andPer2mRNA Levels in the Suprachiasmatic Nuclei

Horikawa, Kazumasa; Yokota, Shigeru; Fuji, Kazuyuki; Akiyama, Masashi; Moriya, Takuya; Okamura, Hitoshi; Shibata, Shigenobu

doi:10.1523/jneurosci.20-15-05867.2000

Cited by 179 publications

(149 citation statements)

References 54 publications

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“…However, it should be noted that photic phase shifts involve an increase in Per1 mRNA expression in the SCN, especially in the calbindin subregion, and that this increase is attenuated by administration of calbindin antisense oligonucleotides (Hamada et al, 2003). Because induction of phase shifts by 8-OH-DPAT injection or other nonphotic signals is associated with decreased Per1 mRNA expression (Horikawa et al, 2000;Fukuhara et al, 2001;Hamada et al, 2004), it is not surprising that calbindin antisense oligonucleotide attenuation of SCN Per1 expression does not prevent phase shifts to 8-OH-DPAT (Hamada et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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Aging affects several processes modulated by the 5-HT 7 receptor subtype, including circadian rhythms, learning and memory, and depression. Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT 7 receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection. To elucidate the mechanisms underlying the aging decrease in 5-HT 7 receptors, we investigated aging modulation of 5-HT 7 receptor mRNA expression in the DRN, brain regions afferent to the DRN, and brain regions regulating circadian rhythms or memory. In situ hybridization for 5-HT 7 receptor mRNA was performed on coronal sections prepared from the brains of young, middle-aged, and old male Syrian hamsters. 5-HT 7 receptor mRNA expression was quantified by densitometry of X-ray film autoradiograms. The results showed that aging did not significantly affect 5-HT 7 receptor mRNA expression in the DRN or most other brain regions examined, with the exception of the cingulate cortex and paraventricular thalamic nucleus. Within the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals, 5-HT 7 receptor mRNA expression was localized in a discrete subregion resembling the calbindin subnucleus previously described. A second experiment using adjacent tissue sections showed that 5-HT 7 receptor mRNA and calbindin mRNAs were concentrated in the same region of the SCN, and as well as in the same region of several other brain structures. The localization of 5-HT 7 receptors and calbindin mRNAs within the same regions suggests that proteins they encode may interact to modulate processes such as circadian timekeeping.

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Section: Discussionmentioning

confidence: 99%

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Duncan

Franklin

2007

Brain Research

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“…The effects of serotonin may be partially mediated by the 5HT1A receptor, which is expressed as a post-synaptic receptor in the SCN and as both a post-synaptic and an autoreceptor in the raphe nucleus. Serotonin (5HT) itself and synthetic agonists are able to phase shift the circadian rhythm during the subjective day and attenuate light-induced phase shifting during the subjective night in hamsters (Bobrzynska et al, 1996;Gannon and Millan, 2006;Horikawa et al, 2000;Rea et al, 1994;Tominaga et al, 1992). Furthermore, there have been several reports of 5HT1A antagonists potentiating the phase advance to light, suggesting that serotonergic tone on this receptor normally provides an inhibitory input to the SCN (Gannon, 2003;Gannon and Millan, 2006;Rea et al, 1995;Lall and Harrington, 2006).…”

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confidence: 99%

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

2008

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Health problems can arise from de-synchrony between the external environment and the endogenous circadian rhythm, yet the circadian system is not able to quickly adjust to large, abrupt changes in the external daily cycle. In this study, we investigated the ability of to potentiate the circadian rhythm response to light as measured by phase of behavioral activity rhythms. (5 mg/kg, i.p.) was able to significantly potentiate the response to light both in dark-adapted and entrained hamsters. Furthermore, was effective even when administered up to 6 hours after light onset. Response to a light pulse was both greater in magnitude and involved fewer unstable transient cycles. Finally, was able to speed re-entrainment to a 6 h advance of the light: dark cycle by an average of 6 days when compared to vehicle-treated animals. This work suggests that compounds like NAN-190 may hold great potential as a pharmaceutical treatment for jetlag, shift work, and other circadian disorders. Keywordsserotonin; circadian; light; rhythm; jet-lag; phase shift; transient; entrainment Circadian rhythms are endogenously generated rhythms that coordinate processes such as hormone release, digestive enzyme secretion, and the sleep/wake cycle. In mammals, the major pacemaker is located in the suprachiasmatic nucleus (SCN) in the brain, which uses environmental cues to synchronize, or entrain, internal rhythms to the external surroundings (Rusak and Zucker, 1979; Ralph et al., 1990). Jetlag occurs when internal circadian rhythms become desynchronized from the external time. In humans, this desynchronization results in acute negative effects such as lowered performance levels on the job, difficulty sleeping at the appropriate times, and gastrointestinal problems. If frequent or prolonged, circadian desynchrony may be associated with more chronic health problems in people such as increased risk of breast cancer, cardiovascular disease, reproductive difficulties and peptic ulcers (Knutsson, 2003;Megdal et al., 2005). Studies using laboratory animals even link jetlag with increased rate of tumor growth and increased mortality in aged mice (Davidson et al., 2006;Filipski et al., 2004). Given the detrimental effects, studies have investigated several different methods to reduce circadian desynchrony. Melatonin, exposure to bright light, and gradual shifting of the sleep/wake cycle prior to jet travel in varying combinations have all been shown *Corresponding author. Tel: 1-413-585-3925; fax: 1-413-585-3786. E-mail address: mharring@email.smith.edu (M. Harrington). 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 ...

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“…Similarly, benzodiazepines also entrain the circadian rhythm of the SCN when injected late at night (60). In hamsters, serotonin 1a/7-receptor agonists phase-advance the circadian locomotor activity rhythm by reducing Per1 and Per2 gene expression in the SCN (61). Lithium lengthens the locomotor activity rhythm in rodents by inhibiting GSK3b in the SCN (51).…”

Section: Neuropharmacologymentioning

confidence: 99%

Chrono-biology, Chrono-pharmacology, and Chrono-nutrition

Tahara¹,

Shibata²

2014

J Pharmacol Sci

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Molecular mechanisms of the circadian clock systemThe circadian clock system has been widely maintained in many species, from prokaryotes to mammals. "Circadian" means "around [a] day" in Latin, and therefore "circadian rhythm" refers to a cycle of approximate 24 h. The earth rotates once every 24 h, and the circadian system has evolved to adjust functions and behavior to this cycle in order to efficiently utilize sunlight for photosynthesis in the case of plants and cyanobacteria and to obtain food in the case of animals. One of the most important features of our circadian system is that circadian clocks can endogenously maintain time under constant darkness and without external stimuli, suggesting that our body has its own internal clocks. In 1972, Moore and Eichler (1) investigated the effects of destroying the suprachiasmatic nucleus (SCN) in the rat hypothalamus. Their results revealed the loss of sleep-wake cycles and corticosterone rhythms. Since then, the SCN is regarded as the location of the master clock system in mammals. The SCN receives light-dark information directly through the retinal-hypothalamic tract and organizes the local clock in the peripheral tissues through multiple pathways involving neural and hormonal functions (2, 3). The molecular mechanism of the circadian system in mammals has been well studied over the past two decades. The transcriptional-translational feedback loop of the major clock genes Bmal1, Clock, Per1/2, and Cry1/2 is the main component of the circadian system (2) (Fig. 1A). Bmal1 and Clock, which are transcriptional activators, play a positive role in activating the Per and Cry genes through a specific promoter sequence known as the E-box. Per and Cry are translated into proteins in the cytoplasm and are then transported back into the nucleus after interacting with each other, and they subsequently stop their transcription by binding to BMAL1 and CLOCK. Thus, Per and Cry are rhythmically expressed over a 24-h period. This transcriptional regulation induces rhythmic expression of approximately 10% of all genes in each peripheral cell (4 -6). In addition to such transcriptional regulation of the circadian clock, post-transcriptional regulation and translational regulation have recently been reported to play important roles in maintaining circadian rhythms. Genome-wide RNA-seq and Chip-seq analyses found that only 22% of the rhythmically oscillating messenger RNAs are driven by de novo transcription, with RNA polymerase II recruitment and chromatin remodeling also exhibiting such rhythms (7). Furthermore, it was reported that the non-transcriptional redox cycle has a 24-h rhythm in Chrono-biology, Chrono-pharmacology, and Chrono-nutrition Tokyo 162-8480, Japan Received October 25, 2013; Accepted January 5, 2014 Abstract. The circadian clock system in mammals drives many physiological processes including the daily rhythms of sleep-wake behavior, hormonal secretion, and metabolism. This system responds to daily environmental changes, such as the light-dark cycle, food...

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Nonphotic Entrainment by 5-HT_1A/7Receptor Agonists Accompanied by ReducedPer1andPer2mRNA Levels in the Suprachiasmatic Nuclei

Cited by 179 publications

References 54 publications

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

Expression of 5-HT7 receptor mRNA in the hamster brain: Effect of aging and association with calbindin-D28K expression

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

Chrono-biology, Chrono-pharmacology, and Chrono-nutrition

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