No description available.

Subjective feeling, or mood, is not just a product of situational and dispositional factors, but is also based in part on underlying circadian rhythms. Notably, accumulating evidence suggests that circadian patterning is limited to positive affect, possibly as an adaptive manifestation of an appetitive motivational system. Furthermore, dispositional factors may influence the observed patterning, such as blunting the rhythm in positive affect when depression is present. The present study sought to examine further these phenomenon at an individual-level, as well as to explore circadian and affective interactions at a couple-level for perhaps the first time by monitoring mood, interpersonal interactions, sleep, activity, and light in 31 bed-sharing cohabitating couples over the course of 7 days. Participants' depression, well-being, relationship satisfaction, and morningness-eveningness were also assessed. Systematic daily patterning was found in all three measures of affect, and was moderated by depression, well-being, and morningness-eveningness. Within-couple affective synchrony (covariation) was positively associated with relationship satisfaction, within-couple morningness-eveningness similarity, and synchrony of sleep timing. Finally, day-to-day within-couple sleep timing synchrony predicted the tenor of the following day's partner interactions and affect. These data provide further evidence of potentially important interactions between sleep, circadian, affective processes both within- and between-individuals.

No description available.

Vitamin A is an essential dietary component which primarily acts through its active metabolite, retinoic acid (RA), a potent transcriptional regulator that also has non-genomic activities. There is increasing evidence for a role for vitamin A in the regulation of circadian rhythms, and previous studies suggest that it serves important roles in the pineal gland, an integral component of the circadian system due to its function of melatonin production. However very little is currently known about how these effects are mediated, or about RA signalling in the pineal gland. This study aimed to establish whether RA is synthesised in the rat pineal gland and determine its role here. This included investigating whether RA is subject to diurnal changes in synthesis and signalling, and examining its involvement in the key rhythms in this gland: melatonin synthesis, kinase activation and clock gene expression. Organotypic culture of rat pineal glands, qPCR and western blotting were among the techniques employed to do this, as well as RA quantification using a reporter cell line. The rat pineal gland was found to produce RA and robust diurnal changes in synthesis were detected. Furthermore, diurnal changes in expression of RA signalling genes suggested there are corresponding changes in RA activity. RA was not found to rapidly regulate Aanat transcription, melatonin synthesis or clock gene expression in vitro, however it was found to rapidly down-regulate extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Furthermore, strong cytoplasmic expression of RA receptor α was detected in pinealocytes. These results suggest RA has a non-genomic role in the pineal gland and may be involved in driving the diurnal rhythm in kinase activation.

Abstract not available

Circadian rhythms are the endogenous cycling of hormones, activity patterns and gene expression that occur across 24 hours. Disruption of circadian rhythms has been associated with multiple health complications, including reduction of fertility. The bmal1 mouse provides an animal model for central and peripheral loss of rhythmicity. Herein the reproductive function and postnatal development in the bmal1 knockout mouse has been evaluated. The reproductive capability of the heterozygous breeding colony was investigated, with around 50% of the female breeder mice becoming pregnant within one estrus cycle. The offspring of the colony had a higher than expected level of perinatal mortality while the knockout and heterozygous genotype was under represented among the offspring surviving to weaning, suggesting high knockout embryo or perinatal losses. The circadian phenotype of this mouse model was confirmed, identifying the severe disruption of circadian behavioural rhythms. Further, the growth of the bmal1 knockout mice was retarded compared with their heterozygous and wild type littermates from weaning to 9 months of age. The reproductive function of the homozygous male bmal1 knockout mouse was evaluated. They showed poor fertility, poorly developed secondary sexual organs, reduced sperm count and reduced sperm motility. Female bmal1 knockout mice had delayed vaginal opening, delayed onset of first estrus, disrupted estrus cyclicity as well as impaired reproductive and mammary tissue development. Steroid hormone synthesis was compromised in both males (testosterone) and females (progesterone) and ovarian morphology revealed reduced corpora lutea formation and structural abnormalities. Female bmal1 knockout mice also evidenced profound infertility, which was caused by a continuum of reproductive insufficiencies including reduced ovulation of oocytes, poorer progression of the preimplantation embryo and failure to successfully implant in the uterus. While the ovaries of bmal1 knockout females were able to respond to exogenous stimulation, the number of ovulated oocytes was reduced, the fertilised oocytes were of reduced quality, progressed poorly to mature blastocyst and once again failed to implant. A bioinformatical evaluation of a panel of genes closely involved in reproduction and ovarian function was analysed for the presence of circadian enhancer regions (E-box sequences) or RORA response elements (RRE) in their promoter regions. It was revealed that many of the genes investigated contained one or more circadian E-box and RRE sequence, providing a mechanism for the disruption of circadian gene expression within the ovary to cause detrimental changes in gene expression. Further to this, the gene expression profile of these functional genes and clock genes were evaluated in ovarian tissues from wild type and knockout mice across the estrus cycles and across 24 hours. It was shown that the murine ovary rhythmically expressed the genes involved with the molecular clock across 24 hours, as well as several other genes previously associated with rhythmicity in peripheral tissues. Further, the loss of functional bmal1 gene expression resulted in up or down regulation of over 75% of the functional genes investigated, including steroidogenic acute regulatory protein (the rate limiting enzyme for progesterone synthesis). In conclusion, the bmal1 knockout mouse shows a significant multi-factorial loss in fertility in both males and females. This loss occurs across a range of tissues and results in heavily reduced fertility in the male and complete infertility in the female. Further research could identify in greater detail the precise molecular mechanisms underpinning of this disruption. / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

Canadians live in a society where the sun does not dictate the workday. Our lifestyles must shift to cater to the 24-hour demands of a fast paced global community. As a result our circadian rhythms are altered, leading to dysregulation of key physiological processes responsible for the maintenance of essential functions like energy homeostasis. Energy homeostasis is controlled by neuropeptide-expressing neurons within the hypothalamus. These neurons are affected by circulating hormone and nutrient levels in addition to their endogenous molecular clock machinery that controls cellular processes. Therefore, hypotheses were generated that non-SCN hypothalamic neurons express orexigenic neuropeptides in a rhythmic fashion without external influence from the SCN as a result of internal rhythmicity; and that elevated concentrations of palmitate, a ubiquitous saturated FFA common in a high fat diet, have direct influence on the mRNA levels of circadian clock components Bmal1, Clock, Per2, Rev-erbα and the potent orexigenic neuropeptides NPY, AgRP and ppGhrelin through mechanisms related to HAT, SIRT1 and AMPK. Using the mHypoE-44 neurons, a well characterized cell line that expresses the molecular clock and specific neuropeptides these hypotheses were explored in four studies. Neuropeptide expression within the mHypoE-44 neurons was determined to be rhythmic. NPY and NT demonstrate significant 24-hour rhythms. CRH and ppGhrelin mRNA cycled significantly in an ultradian fashion, oscillating approximately every 18 h. AgRP mRNA did not show a significant rhythm. We identified rhythmic binding of BMAL1 to the NPY promoter, suggesting clock-mediated control of neuropeptide expression. Bmal1 and Clock mRNA levels were elevated with palmitate, whereas Per2 and Rev-erbα mRNA showed significant decreases following palmitate treatment. Palmitate increased the acetylation of both BMAL1 and PER2 proteins. Alteration of AMPK activity altered the mRNA levels of all clock genes assayed and AMPK activation diminished the palmitate-induced changes in Bmal1 mRNA. Palmitate significantly elevated both NPY and ppGhrelin mRNA levels. Chemical modifiers that decrease acetylation altered these systems. AMPK activation reduced the palmitate-induced changes in NPY mRNA levels. These findings demonstrate that non-SCN neurons have rhythmic neuropeptide transcript levels. This thesis elucidates a direct effect of palmitate on the molecular clock and neuropeptide expression at the level of the hypothalamic neuron; and these findings highlight a role for HAT/SIRT1 activation and AMPK in these important processes, which ultimately contribute to the understanding of circadian dysregulation and energy balance.

Canadians live in a society where the sun does not dictate the workday. Our lifestyles must shift to cater to the 24-hour demands of a fast paced global community. As a result our circadian rhythms are altered, leading to dysregulation of key physiological processes responsible for the maintenance of essential functions like energy homeostasis. Energy homeostasis is controlled by neuropeptide-expressing neurons within the hypothalamus. These neurons are affected by circulating hormone and nutrient levels in addition to their endogenous molecular clock machinery that controls cellular processes. Therefore, hypotheses were generated that non-SCN hypothalamic neurons express orexigenic neuropeptides in a rhythmic fashion without external influence from the SCN as a result of internal rhythmicity; and that elevated concentrations of palmitate, a ubiquitous saturated FFA common in a high fat diet, have direct influence on the mRNA levels of circadian clock components Bmal1, Clock, Per2, Rev-erbα and the potent orexigenic neuropeptides NPY, AgRP and ppGhrelin through mechanisms related to HAT, SIRT1 and AMPK. Using the mHypoE-44 neurons, a well characterized cell line that expresses the molecular clock and specific neuropeptides these hypotheses were explored in four studies. Neuropeptide expression within the mHypoE-44 neurons was determined to be rhythmic. NPY and NT demonstrate significant 24-hour rhythms. CRH and ppGhrelin mRNA cycled significantly in an ultradian fashion, oscillating approximately every 18 h. AgRP mRNA did not show a significant rhythm. We identified rhythmic binding of BMAL1 to the NPY promoter, suggesting clock-mediated control of neuropeptide expression. Bmal1 and Clock mRNA levels were elevated with palmitate, whereas Per2 and Rev-erbα mRNA showed significant decreases following palmitate treatment. Palmitate increased the acetylation of both BMAL1 and PER2 proteins. Alteration of AMPK activity altered the mRNA levels of all clock genes assayed and AMPK activation diminished the palmitate-induced changes in Bmal1 mRNA. Palmitate significantly elevated both NPY and ppGhrelin mRNA levels. Chemical modifiers that decrease acetylation altered these systems. AMPK activation reduced the palmitate-induced changes in NPY mRNA levels. These findings demonstrate that non-SCN neurons have rhythmic neuropeptide transcript levels. This thesis elucidates a direct effect of palmitate on the molecular clock and neuropeptide expression at the level of the hypothalamic neuron; and these findings highlight a role for HAT/SIRT1 activation and AMPK in these important processes, which ultimately contribute to the understanding of circadian dysregulation and energy balance.

The ubiquity of circadian systems has allowed their characterization in a broad range of model systems, which has greatly improved knowledge of how these systems are organized and the vast range of cellular and organismal processes under circadian control. Most of the advances, however, have come in describing the central oscillators of these systems, and, in some cases, the input pathways used to coordinate these oscillators to external time. Very little progress has been made in understanding the output pathways that allow circadian systems to regulate the breadth of processes shown to be clock-controlled. A genetic selection was designed to obtain mutations in genes involved in circadianregulated expression of the Neurospora crassa ccg-1 and ccg-2 genes. Some, but not all, of the strains obtained display altered regulation of more than one ccg as well as an ‘Easlike’ appearance on solid media, and altered circadian period on race tubes. The data suggest a model in which output from the clock to these two genes is through a single, bifurcated pathway. The cloning of the gene mutated (rrg-1) in one of the strains from the above selection led to the first molecular description of a circadian output pathway in Neurospora, the HOG MAP kinase pathway. The HOG pathway has been previously described with regard to its role in the osmotic-stress response. The discovery of the involvement of rrg-1 in circadian regulation of ccg-1 and ccg-2 led to the discovery of regulation of the HOG pathway by the circadian clock. The data indicate that osmotic stress information and time-of-day information are transduced through the HOG pathway and implicate a role for the clock in preparing the organism for daily occurrences of hyperosmotic stress associated with sun exposure. The genetic selection, and the description of the HOG pathway with regard to circadian output, provide a basis for further characterization of circadian output in Neurospora. The ubiquity of MAP kinase pathways, such as the HOG pathway, and the observed similarities in the mechanisms of circadian clock function across multiple phyla, indicate that these findings may well be applicable to other model systems.

Thesis (M. Sc.)--York University, 1999. Graduate Programme in Biology. / Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ43394.