Human circadian rhythms

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Cajochen C, Krauchi K, Wirz-Justice A (2003) Role of melatonin in the regulation of human circadian rhythms and sleep. J Neuroendocrinal 15 432-437... 

Cermakian N, Boivin DB (2003) A molecular perspective of human circadian rhythm disorders. Brain Res Brain Res Rev 42 204-220... 

Wever, R. Effects of lov-level, low-frequency fields on human circadian rhythms. Neurosci. Res. Program Bull. 1977, 15, 39-45. 

In humans, circadian rhythms governed by the SCN affect a large number of physiological functions, including the sleep-wake cycle and nutrition (Moore-Ede et al, 1982 Touitou Haus, 1992). Moreover, a variety of hormone levels (Van Cauter Aschoff, 1989) or enzyme activities display circadian patterns. Circadian rhythms, accordingly, play important roles in both health and disease (Moore-Ede, Czeisler Richardson, 1983). Clinical applications of circadian rhythm research include the use of light to treat maladaptation to night work (Czeisler et al, 1990), jet lag, or seasonal affective disorder (Lewy et al, 1987). 

Kronauer, R.E. 1984. Modeling principles of human circadian rhythms. In Mathematical Models of the Circadian Sleep/Wake Cycle, M.C. Moore-Ede C.A. Czeisler, eds. Raven Press, New York, pp. 105-28. 

At its most fundamental level, the circadian cycle rests on the influence of so-called clock genes . These genes have been studied most extensively in insects but they have also been found in humans. Their protein products enter the cell nucleus and regulate their own transcription. This feedback process is linked to exposure to light and so it is not surprising that visual inputs are important for maintenance of circadian rhythms. However, it is not the reception of specific visual information, transmitted in the optic nerve to the lateral geniculate nucleus (LGN) and visual cortex (i.e. visual discrimination), that is responsible for the rhythm but the more simple, almost subconscious, reception of light. 

Folate and FAD are also components of cryptochromes, proteins widespread in living organisms. Cryptochromes are considered photolyase sequence homologues with no DNA repair activities but with blue light-activated factors. Cryptochromes regulate growth and development in plants and seem to be responsible for the synchronization of circadian rhythms in animals and human. ... 

Melatonin secretion is synchronized to the light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) and low diurnal baseline levels (about 10 pg/ml plasma). Studies have supported the value of the exogenous administration of melatonin in circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders of the immune function, and oxidative damage (Karasek et al. 2002 Pandi-Perumal et al. 2005, 2006 Srinivasan et al. 2005a,b, 2006 Hardeland et al. 2006). 

Dijk, D. J. Czeisler, C. A. (1994). Paradoxical timing of the circadian rhythm of sleep propensity serves to consolidate sleep and wakefulness in humans. Neurosci. Lett. 166, 63-8. 

To mimic melatonin action and increase the half-life is the goal of melatonin receptor agonists, which are the more recent addition to the insomnia therapeutic armamentarium. These compounds, in addition to use for insomnia, may have potential application in the synchronization of disturbed circadian rhythms, sleep disturbances in the elderly, seasonal depression and jet lag, to name a few. Furthermore, studies have shown that melatonin receptor agonists do not induce any of the hypothermic, hypotensive or bradycardic effects caused by melatonin in humans [27,28]. 

Serotonin 5-HT1A Human cDNA Alzheimer s disease, anxiety, depression, schizophrenia, hypertension, inflammation, pain, migraine, spasticity ulcers, obesity glaucoma Somatodendritic autoreceptor in hippocampus and raphe nuclei, circadian rhythm, somatodendritic heteroreceptor at cholinergic terminals of myenteric plexus... 

The results obtained with the model for the mammalian circadian clock provide cues for circadian-rhythm-related sleep disorders in humans [117]. Thus permanent phase shifts in LD conditions could account for (a) the familial advanced sleep phase syndrome (FASPS) associated with PER hypopho-sphorylation [118, 119] and (b) the delayed sleep phase syndrome, which is also related to PER [120]. People affected by FASPS fall asleep around 7 30 p.m. and awake around 4 30 a.m. The duration of sleep is thus normal, but the phase is advanced by several hours. Moreover, the autonomous period measured for circadian rhythms in constant conditions is shorter [121]. The model shows that a decrease in the activity of the kinase responsible for PER phosphorylation is indeed accompanied by a reduction of the circadian period in continuous darkness and by a phase advance upon entrainment of the rhythm by the LD cycle [114]. 

R. E. Kronauer, D. B. Forger, and M. E. Jewett, Quantifying human circadian pacemaker response to brief, extended, and repeated light stimuli over the phototopic range. J. Biol. Rhythms 14, 500-515 (1999). 

C. R. Jones, S. S. Campbell, S. E. Zone, E. Cooper, A. DeSano, P. J. Murphy, B. Jones, L. Czajkowski, and L. J. Ptacek, Familial advanced sleep-phase syndrome A short-period circadian rhythm variant in humans. Nat. Med. 5, 1062-1065 (1999). 

Panda S, Hogenesch JB, Kay SA 2002a Circadian rhythms from flies to human. Nature 417 329-335... 

Camacho F, Cilio M, Guo Y et al 2001 Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. FEES Lett 489 159-165 Delaunay F, Thisse C, Marchand O, Laudet V, Thisse B 2000 An inherited functional circadian clock in zebrafish embryos. Science 289 297-300 Dunlap J 1998 Circadian rhythms. An end in the beginning. Science 280 1548-1549 Ebisawa T, Uchiyama M, Kajimura N et al 2001 Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. EMBO Rep 2 342-346 Edery I, Zwiebel LJ, Dembinska ME, Rosbash M 1994 Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci USA 91 2260-2264 Ishida N, Kaneko M, AUada R 1999 Biological clocks. Proc Natl Acad Sci USA 96 8819-8820... 

Ishida N, Miyazaki K, Sakai T 2001 Circadian rhythm biochemistry from protein degradation to sleep and mating. Biochem Biophys Res Commun 286 1—5 Kloss B, Price JL, Saez L et al 1998 The Drosophila clock gene double-time encodes a protein closely related to human casein kinase lepsilon. Cell 94 97—107 Lau LF, Nathans D 1987 Expression of a set of growth-related immediate early genes in BALE/ c 3T3 cells coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci USA 84 1182-1186... 

Naidoo N, Song W, Hunter-Ensor M, Sehgal A 1999 A role for the proteasome in the light response of the timeless clock protein. Science 285 1737-1741 Panda S, Hogenesch JB, Kay SA 2002 Circadian rhythms from flies to human. Nature 417 ... 

In addition, the neuroanatomy of OT receptor distribution patterns is species-specific. Wide variability in patterns of receptor distribution exists across even closely related species (Insel and Shapiro, 1991 Insel et al., 1999). These cross-species disparities necessitate caution when one makes general statements about the relationships between OT and specific behaviors. For example, primates and humans have a circadian rhythm of CSF OT, while rodents do not (McCarthy and Altemus, 1997). There are important limits to the extent to which the results of specific gene knockout models may be extrapolated to other species. Ultimately, primate models may be necessary to assess the functions of OT in the primates and humans. 

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