Thesis (Ph.D.)--Kent State University, 2009. / Title from PDF t.p. (viewed Apr. 15, 2010). Advisor: J. David Glass. Keywords: Suprachiasmatic nucleus; serotonin; nonphotic; arginine vasopressin; hamster. Includes bibliographical references (p. 91-111).

Thesis (Ph. D.)--University of California, San Diego, 1997. / Vita. Includes bibliographical references (leaves 108-111).

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2006. / Title from title screen (site viewed June 11, 2007). PDF text: viii, 133 p. : ill. UMI publication number: AAT 3239364. Includes bibliographical references. Also available in microfilm and microfiche formats.

No description available.

Circadian rhythms are known to be entrained to the 24 hour day through interactions between endogenous mechanisms and a number exogenous factors that include the light-dark cycle and social interaction. Intensive care patients are thought to be prone to disturbances in their circadian rhythms due to isolation from environmental changes and sensory deprivation as a result of sedation and sleep disturbance. The main aim of this thesis was to determine whether circadian rhythms in critically ill patients are desynchronised from the environment in comparison with those observed in healthy individuals, using urinary aMT6s excretion, plasma melatonin and core body temperature as markers of the endogenous clock. Patients in the Intensive Care Unit (ICU) at the Royal Free Hospital, London, who were stable, inotrope-free, not undergoing haemodiafiltration and with an ICU stay of more than three days were studied. Cosinor analysis of retrospective core body temperature data taken from nursing charts showed that a statistically significant rhythm with a period of 24h was present in 49.5% of the patient days studied. The position of acrophase showed abnormalities within individuals and between individuals. Prospective core body temperature studies confirmed the findings of abnormal circadian rhythmicity but suggested that the rhythms were influenced by fever associated with infection. Urinary 6-sulphatoxymelatonin (aMT6s) excretion data detected rhythmic activity and allowed for the identification of four patterns of excretion rate over 24h: normal rhythmicity, phase shifted rhythms, abnormal with frequent fluctuations and abnormal but arrhythmic. Urinary aMT6s excretion rate measured on two or three occasions at weekly intervals identified changes associated with the normalisation of circadian rhythmicity, namely an increase in the amplitude in some patients and the development of significant diurnal changes from grossly abnormal patterns of urinary aMT6s excretion in others. This trend was seen in patients that were improving clinically, but could not be associated with disease severity as determined by APACHE II scoring. Studies on the circadian rhythms of urine volume and creatinine clearance suggested that renal function in the absence of acute renal failure was still impaired or possibly influenced by treatment medication and could modify urinary aMT6s excretion. Measurements of plasma melatonin identified circadian rhythmicity in 7 out of 9 patients of which 5 were significant by cosinor analysis. These 5 patients had plasma melatonin rhythms that were either normal or phase shifted. The circadian rhythms of plasma cortisol, plasma prolactin and plasma TSH in most ICU patients were also abnormal and showed poor correlations with plasma melatonin. Overall this thesis provides evidence of abnormal circadian rhythmicity in critically ill patients and identifies this group of patients as one that might benefit from light or melatonin treatment to help resynchronise rhythms.

No description available.

Circadian rhythms are the outward manifestation of an internal timing system that measures time in 24-hr increments. The mammalian circadian system is hierarchical, with a pacemaker in the suprachiasmatic nucleus (SCN) synchronizing cell-autonomous oscillators in peripheral tissues. Much of what we know about rhythmicity in peripheral tissues comes from studies monitoring bioluminescence rhythms in PERIOD2::LUCIFERASE knock-in mice. A limitation with this model is that rhythmicity cannot be monitored in specific cells due to widespread reporter expression. To address this shortcoming, we generated a mouse that expresses luciferase from the Dbp locus only after Cre-mediated recombination. I validated this conditional mouse to provide a tool for monitoring circadian rhythms in a tissue/cell-specific manner. Crossing the conditional reporter mice with mice expressing Cre recombinase in various cell types allowed detection of rhythmic bioluminescence in the expected tissues, in vivo and ex vivo, as well as in slice cultures containing the SCN. The phase of bioluminescence rhythms from explants of mouse peripheral tissues indicated that DbpLuc/+ bioluminescence rhythms have an earlier phase than PER2::LUC/+ rhythms. Importantly, we confirmed that editing of the Dbp locus did not alter the period of circadian locomotor activity rhythms and did not alter liver Dbp RNA rhythms. Finally, the reporter mouse allows for monitoring rhythms in specific tissues in ambulatory mice. Thus, this mouse line is useful for studying circadian rhythms in a tissue/cell-type specific manner, which can be used to better monitor phase relationships between tissues at baseline and after environmental perturbations that disrupt circadian rhythms.

Circadian Rhythms are the outputs of an internal biological clock common to all animals. Most circadian rhythms have about a 24-hour period and can synchronize with the earth’s solar day. Our lab primarily studies the circadian rhythms of spiders because their internal clocks can be extremely different from 24 hours (some as much as five hours different), yet they can remain synchronized with the solar day. The objective of this study is to identify a non-spider species for comparison with spiders that, a) has a clear and measurable circadian rhythm, and b) can easily be bred and reared in the lab. Gromphadorhina Grandidieri, also known as Black Tiger Hissing Cockroach (hereafter referred to as ‘hissers’), is one of the very many species of African Hissing Cockroaches native to rainforests in Madagascar. These species get the nickname ‘hisser’ because of their defense mechanism that forces air through spiracles which are breathing holes in the exoskeleton to make a hissing noise like a cat would. These animals are colonial and are easily bred and reared in captivity. Our hypotheses were that G. Grandidieri will be nocturnally active with a typical animal circadian rhythm of close to 24 hours. To carry out this experiment we measured locomotor activity in Juvenile and adult hissers for 5 days in a 12:12 hour light:dark cycle followed by 7-10 days in constant darkness to reveal the animals’ internal clock period. We measured this using an activity monitor which records when an individual moves across an infrared light beam. Data were taken from 32 individuals in this manner. Our results showed that juveniles had a mean circadian rhythm of 24.03 + 0.49 hours, and that adults had a mean rhythm of 24.12 + 0.90 hours. Most, but not all, individuals had a clear and measurable circadian rhythm and survived the duration of the experiment. Locomotor activity in the light:dark cycle was mainly in the dark phase, confirming that these animals are generally nocturnal. Overall, our hypotheses were supported and we have identified an excellent comparison species for future research in our lab.

Postpartum depression (PPD) remains a serious mood disorder without a known etiology. PPD has a prevalence of 7-15% in the general population. Women with a history of a mood disorder are at an even higher risk for the development of PPD. Work over the last few decades has established a strong association between circadian rhythm and sleep disturbances and mood disorders, such as Major Depressive Disorder (MDD) and Bipolar Disorder (BD). Despite the breadth of evidence associating circadian rhythm disruption and depressive mood episodes, literature establishing a connection between circadian rhythms and changes in mood across the perinatal period is lacking. The work outlined in this thesis aimed to address this gap by examining the association between circadian rhythm and sleep disturbances across the perinatal period and their association with changes in mood in women at high and low risk of PPD development. A total of 87 women were studied, 45 healthy controls and 42 women with a mood history. Women were interviewed during the third trimester of pregnancy and between six to twelve weeks postpartum. Sleep and circadian rhythms were measured using both subjectively with self-reported questionnaires and objectively with actigraphy. Our results show that women at high and low risk showed higher disruption differ in subjective circadian rhythmicity, as well as in both subjective and objective parameters of sleep. Specifically, women at high risk for postpartum were found to have lower sleep efficiency, as measured by actigraphy, in the postpartum. In addition, subjective and objective parameters of sleep and circadian rhythms are associated with changes in depressive symptoms across the perinatal period. Our findings suggest that stabilizing circadian rhythms and improving sleep quality throughout the perinatal period can prevent postpartum mood worsening, particularly for those women at greatest risk. / Thesis / Master of Science (MSc)

Circadian rhythms are periodic physiological events that recur about every 24 hours. The word circadian derives from the Latin words <i>circ</i>a "about" and <i>dies</i> "day". The importance of circadian rhythms is well recognized in many different organisms' survival as well as in human physiology. It was in the 1950's that scientists demonstrated the existence of an endogenous biological clock, and that the clock is temperature compensated. However, the molecular mechanism of circadian rhythms began to come clear only after the discovery of the period (per) gene in Drosophila melanogaster in 1971, and the frequency (frq) gene in Neurospora crassa in 1973. Since the breakthrough discoveries of the per and frq genes and their mutants (short period mutants, perS or frq1, frq2; and long period mutants perL or frq3, frq7), molecular biologists have discovered other crucial components of the mechanism of circadian rhythms. Currently, there are about a dozen identified circadian genes in Drosophila melanogaster. The consensus idea of the mechanism is that it involves two-interlocked feedback loops largely based on transcription-translation controls. However, based on our mathematical models and analysis, we propose that there is also an autocatalytic effect based on proteolysis and stabilization of PER proteins. Based on the dynamics of multiple steady states and limit cycle oscillation, we propose an alternative mechanism for robust temperature compensation. We start with a simple model in order to understand the core dynamics of the clock mechanism, and move to a more comprehensive model. In both cases, we use bifurcation analysis as a tool to understand the dynamics of the system. With our model, we propose hypotheses to be tested in Neurospora crassa. / Ph. D.