Saudi Cultural Missions Theses & Dissertations
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Item Restricted The destruction of ultradian and circadian rhythms(Lancaster University, 2024) Alanazi, Mansour Awadh; Stefanovska, AnetaOne of the most generally recognised rhythms observed across various living creatures is the circadian rhythm, a recurrent biological activity lasting around 24 hours. It is said to have evolved in reaction to the regular environmental alternation of light and darkness. Pacemaker cells, which are thought to be critical in generating the circadian rhythm, have been identified in suprachiasmatic nucleus (SCN) in 1972. However, there is ongoing discussion about whether the circadian rhythm is a truly basic rhythm generated in the SCN, or whether alternative mechanism are involved in its modulation. Arousing stimuli, such as scheduled feeding, running wheel access, or methamphetamine (MA) administration, represent non-canonical circadian processes. Here, we investigate the circadian rhythm in genetically modified mice with the Per1/2/3 genes knocked out, resulting in a disturbance of this rhythm, as Per1/2/3 genes are essential components of the mammalian canonical circadian mechanism. Additionally the effect of MA, a potent central nervous system stimulant, was evaluated on Per1/2/3 genes knock out mice. As a reference, a group of wild-type mice was also recorded. In each case wheel running activity was recorded every minute for a period of 4 to 9 weeks. The investigation aimed to deduce whether rhythms remained when the clock genes were disabled and how MA affects them. Nonlinear time-series analysis methods, specifically developed for analysis of oscillatory processes with time-varying frequencies, where used to analyse the recorded time series. We show that MA restores the circadian rhythm and increases the total power. Moreover, the rhythm gets more irregular with MA administration compared to the wild-type case. Additionally, MA introduces a new circabidian rhythm at around 40 hours. In addition to the power analysis, couplings between rhythms on different timescales were considered. Firstly, harmonic analysis was performed to deduce which of the observed oscillations result from independent modes. This analysis revealed that, in all Per1/2/3 knock out mice not exposed to MA, there is a harmonic relationship between the 7 and 3.5 hour cycles. Following this, to elucidate the coupling between the remaining independent modes, bispectral analysis and dynamic Bayesian inference were applied. The Per1/2/3 knocked out mice exposed to MA exhibited coupling between ∼24 hours and ∼1 hour oscillations, while in the Per1/2/3 knocked out mice not exposed to MA a coupling between ∼8 hours and ∼1 hour oscillations was observed. This study revealed the relationship between oscillators in the absence of a canonical circadian clock as well as the effect of MA. Power and coupling analyses provide a useful approach for understanding the functional significance of behavioural rhythms. Such investigations are vital, as disruptions in circadian rhythms are implicated in various diseases, including cancer, obesity, and mood disorders. Based on the obtained results a phenomenological model was developed. It elucidates the dynamic characteristics of circadian rhythms in Per1/2/3 knockout mice, particularly focusing on the alterations induced by methamphetamine exposure. The model captures the time-varying nature of oscillations and their interactions, providing insights into the underlying mechanisms of circadian regulation and potential implications for behavioural health.3 0Item Restricted Alterations of Gut Microbiota due to External Stress and the Associated Health Outcomes – A Systematic Review(University of Aberdeen, 2023-01-18) Almubarak, Fatimah; MacCallum, DonnaBackground. Alterations of gut microbiota have been investigated for their association with many pathologies. Studies have reported significant changes to the composition and diversity of gut microbiota due to external stress using 16S ribosomal RNA sequencing. However, the threat of those alterations to the host's health is poorly studied. This systematic review was performed to explore the associated health outcomes with alterations of gut microbiota in mice exposed to external stresses. Methods. The database PubMed was searched for primary research papers published between 2013 and 2023, for case–control studies detecting gut microbiota in mice exposed to psychosocial, dietary, chemical, and environmental stress. The risk of bias in the studies was assessed using SYRCLE. The α-diversity and the abundance of gut microbiota in mice in stress groups compared to control groups were analysed qualitatively. Results. Eleven studies involving male or female mice were included. The risk of bias in the studies ranged from low to moderate risk. Faecal, caecal, and colonic samples showed no significant difference in the α-diversity of gut bacteria in approximately half of the studies and a lower diversity in the other half. Many variations in the abundance of gut bacteria from the same samples at the taxonomic levels of phylum, genus, family, and species. Conclusions. Alterations of gut microbiota were observed in mice after stress exposure and were thought to be associated with increased inflammation and other health outcomes. Further studies are needed to provide more evidence and explanation for the pathologies associated with changes to gut microbiota.16 0