Disease relevance of Circadian Rhythm

• Disruption of the diurnal rhythm of plasma melatonin in cirrhosis [1].
• Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations [2].
• The patients with breast cancer demonstrated a striking correlation between the melatonin diurnal rhythm and the steroid receptor content of the primary tumor [3].
• Site-directed mutagenesis of Synechococcus KaiB confirmed that alanine substitution of residues Lys-11 or Lys-43 in the cleft, or deletion of C-terminal residues 95-108, which forms part of the ridges, strongly weakens in vivo circadian rhythms [4].
• KaiB is a component of the circadian clock molecular machinery in cyanobacteria, which are the simplest organisms that exhibit circadian rhythms [4].

Psychiatry related information on Circadian Rhythm

• The Drosophila takeout gene is a novel molecular link between circadian rhythms and feeding behavior [5].
• Here we report that the acute administration of triazolam, a short-acting benzodiazepine commonly prescribed for the treatment of insomnia, induces a phase-shift in the circadian rhythm of locomotor activity in golden hamsters [6].
• Pineal melatonin may play an important role in regulation of vertebrate circadian rhythms and in human affective disorders [7].
• Prenatally-stressed (PS) rats also show behaviour consistent with depression, including a phase-shift in their circadian rhythm for corticosterone, sleep abnormalities, a hedonic deficit and greater acquisition of learned helplessness under appropriate conditions [8].
• RESULTS: Cortisol levels were significantly lower at awakening, at 8:00 a.m., and at 8:00 p.m. in Holocaust survivors with PTSD than in nonexposed subjects, resulting in a flatter circadian rhythm, similar to what has been observed in aging but different from what has been reported in younger subjects with PTSD [9].

High impact information on Circadian Rhythm

• RNA from two of these genes, per and tim, is expressed with a circadian rhythm [10].
• Molecular and genetic characterizations of circadian rhythms in Drosophila indicate that function of an intracellular pacemaker requires the activities of proteins encoded by three genes: period (per), timeless (tim), and doubletime (dbt) [10].
• Thus, VRI and PDP1, together with dClock itself, comprise a second feedback loop in the Drosophila clock that gives rhythmic expression of dClock, and probably of other genes, to generate accurate circadian rhythms [11].
• We propose that Clock is uniquely able to induce and organize the core elements of interdependent feedback loops necessary for circadian rhythms [12].
• We now report that mice carrying a null mutation of the VPAC(2) receptor for VIP and PACAP (Vipr2(-/-)) are incapable of sustaining normal circadian rhythms of rest/activity behavior [13].

Chemical compound and disease context of Circadian Rhythm

• Twenty-four-hour (circadian) rhythms in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion, motor activity, and oral temperature were studied in 14 normal subjects and ten manic-depressive patients [14].
• Knockout mice showed a normal circadian rhythm in body temperature and motor activity and had normal body temperature responses to fasting, stress, thyroid hormone, and cold exposure [15].
• Several investigators have proposed that diurnal rhythms, particularly that of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), show abnormalities in affective disorders [16].
• Patients with Cushing's syndrome have been identified by an abnormal low-dose dexamethasone suppression test, elevated urine free cortisol (UFC), an absence of diurnal rhythm of plasma cortisol, or an elevated late-night plasma cortisol [17].
• Methamphetamine (MAP) causes the sensitization phenomena not only in MAP-induced locomotor activity, dopamine release, and Fos expression, but also in MAP-induced circadian rhythm [18].

Biological context of Circadian Rhythm

• The promoter regions of the Per1, Per2 and Cry1 genes exhibit circadian rhythms in H3 acetylation and RNA polymerase II binding that are synchronous with the corresponding steady-state messenger RNA rhythms [19].
• Investigations showed that he had circadian rhythms of body temperature, alertness, performance, cortisol secretion, and urinary electrolyte excretion which were desynchronized from the 24-hour societal schedule [20].
• CREB phosphorylation was dependent on circadian time: CREB became phosphorylated only at times during the circadian cycle when light induced IEG expression and caused phase shifts of circadian rhythms [21].
• A potent inhibitor of protein synthesis, anisomycin, was applied (10(-6)M) in 6-hour pulses at specific phases in the circadian rhythm of endogenous compound action potential (CAP) activity recorded from the eye of Aplysia in vitro [22].
• Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. Implications for energy homeostasis and neuroendocrine function [23].

Anatomical context of Circadian Rhythm

• A central pacemaker for the generation of many circadian rhythms in mammals, including the sleep-wake cycle, appears to be located in the suprachiasmatic nucleus, and recent research indicates that both cell bodies and axons containing GABA are present within the bilaterally paired suprachiasmatic nuclei [6].
• Secretory cells of the chicken pineal gland exhibit light-sensitive circadian rhythms in melatonin release that persist in vitro [24].
• The circadian rhythms of sleep, melatonin secretion and body core temperature are thought to be generated by the suprachiasmatic nucleus of the hypothalamus, the anatomic locus of the mammalian circadian clock [25].
• Thus the double amplitude (total extent of variation) of the circadian rhythm in circulating total, T and T helper lymphocytes varied between 0 in March (P greater than 0.30; no rhythm) and up to 46-68% of the 24-h-mean (M) in November, with acrophases (times of maximum, 0) localized in the first half of the night (P less than 0.001) [26].
• High-level expression of the gene is also seen in particular regions of the forebrain involved in the regulation of circadian rhythms, the endocrine system, and olfactory function, not previously identified in this context [27].

Associations of Circadian Rhythm with chemical compounds

• Entrainment of free-running circadian rhythms by melatonin in blind people [28].
• Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone [29].
• CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity [30].
• There is a circadian rhythm in basal vascular tone, due either partly or entirely to increased alpha-sympathetic vasoconstrictor activity during the morning [31].
• Differential circadian rhythms in pineal and hypothalamic 5-HT induced by artificial photoperiods or melatonin [32].

Gene context of Circadian Rhythm

• Mice deficient in both mPer1 and mPer2 do not express circadian rhythms [33].
• Expression of the CCA1 gene is transiently induced by phytochrome and oscillates with a circadian rhythm [34].
• While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation [35].
• FKF1 mRNA levels oscillate with a circadian rhythm, and deletion of FKF1 alters the waveform of rhythmic expression of two clock-controlled genes, implicating FKF1 in modulating the Arabidopsis circadian clock [36].
• Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms [37].

Analytical, diagnostic and therapeutic context of Circadian Rhythm

• Collection of timed aliquots of medium and subsequent analysis for melatonin by radioimmunoassay reveal circadian rhythms of melatonin output by the isolated pineal [38].
• Measurements oof hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained [39].
• After bilateral T1-T2 ganglionectomy, however, melatonin levels were markedly reduced, and the diurnal rhythm was abolished [40].
• We evaluated the diurnal rhythm of PTH in 11 normal healthy male volunteers in our Intensive Physiologic Monitoring Unit [41].
• 3. Onset and/or offset of melatonin secretion were found to coincide with switch-like transitions between distinct diurnal and nocturnal periods of circadian rhythms in core body temperature, sleepiness, power in the theta band of the wake EEG, sleep propensity and rapid eye movement (REM) sleep propensity [42].

References