circadian and Homeostatic Components of Sleep across Sex and Development in the Diurnal Rodent, Octodon degus.

This dissertation examined the impact of sex and development on sleep in the diurnal rodent, Octodon degus. All experiments utilized electrophysiological measures to quantify sleep patterns, brain temperature and locomotor activity (via electroencephalography, thermistor probes, and infrared motion detectors). The descriptive study revealed the diurnal non rapid eye movement sleep (NREMS) patterns of degus and the low levels of rapid eye movement sleep (REMS), with females showing significantly more NREMS amount and consolidation and less REMS compared to males. Sleep intensity (measured by NREMS delta wave activity) was sexually dimorphic, with males demonstrating higher relative levels during the light phase and females exhibiting increases during the dark phase. Circadian gating of sleep was particularly powerful, with both sexes displaying heightened activity around the light-dark transitions. The second set of experiments aimed to elucidate the homeostatic and circadian components of sleep utilizing the 6h sleep deprivation paradigm. Sleep deprivation increased homeostatic drive within both sexes and was mediated by circadian phase. Compensatory mechanisms for sleep recovery differed between sexes, with males demonstrating transient increases in NREMS amount and consolidation while females displayed transitory increases in NREMS consolidation and prolonged elevation of sleep intensity. Lastly, the final experiments aimed to investigate the two components of sleep across development within male degus. While early pubertal degus did not demonstrate a strong preference for diurnal sleep, the rhythmicity of sleep intensity was consistent with previous studies of diurnal mammals. Late pubertal degus demonstrated circadian variation of NREMS and REMS, suggesting there may be a critical window of hormonal influence on sleep within this diurnal rodent. Both age groups displayed significantly increased NREMS parameters in response to a 6h deprivation during the dark phase, yet the circadian component of sleep was dampened during light transition periods, contrasting adult degus patterns. Together, these data highlight Octodon degus as a good diurnal rodent model for investigating the circadian and homeostatic mechanisms of sleep, as well as the interaction of these opponent processes under baseline conditions and following physiological disruption. Furthermore, the slowly developing degu presents a unique opportunity to examine these components in a small diurnal mammal.Ph.D.NeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86406/1/pjamie_1.pd

Plasma sterols and vitamin D are correlates and predictors of ozone-induced inflammation in the lung: A pilot study.

BackgroundOzone (O3) exposure causes respiratory effects including lung function decrements, increased lung permeability, and airway inflammation. Additionally, baseline metabolic state can predispose individuals to adverse health effects from O3. For this reason, we conducted an exploratory study to examine the effect of O3 exposure on derivatives of cholesterol biosynthesis: sterols, oxysterols, and secosteroid (25-hydroxyvitamin D) not only in the lung, but also in circulation.MethodsWe obtained plasma and induced sputum samples from non-asthmatic (n = 12) and asthmatic (n = 12) adult volunteers 6 hours following exposure to 0.4ppm O3 for 2 hours. We quantified the concentrations of 24 cholesterol precursors and derivatives by UPLC-MS and 30 cytokines by ELISA. We use computational analyses including machine learning to determine whether baseline plasma sterols are predictive of O3 responsiveness.ResultsWe observed an overall decrease in the concentration of cholesterol precursors and derivatives (e.g. 27-hydroxycholesterol) and an increase in concentration of autooxidation products (e.g. secosterol-B) in sputum samples. In plasma, we saw a significant increase in the concentration of secosterol-B after O3 exposure. Machine learning algorithms showed that plasma cholesterol was a top predictor of O3 responder status based on decrease in FEV1 (>5%). Further, 25-hydroxyvitamin D was positively associated with lung function in non-asthmatic subjects and with sputum uteroglobin, whereas it was inversely associated with sputum myeloperoxidase and neutrophil counts.ConclusionThis study highlights alterations in sterol metabolites in the airway and circulation as potential contributors to systemic health outcomes and predictors of pulmonary and inflammatory responsiveness following O3 exposure