| dc.description.abstract | The presence and absence of light is a fundamental environmental signal leveraged across the tree of life to synchronize internal biological processes to external, predictable environmental conditions. With the rise of artificial lighting sources and everchanging modern lifestyles, humans and wildlife have been faced with a new challenge – disruption in the nighttime environment through exposure to artificial lighting sources at various spectra, types, intensities, and patterns.
Throughout my PhD, I aimed to elucidate how birds and mammals respond to perturbations in the nighttime environment through aperiodic and alternating lighting conditions, particularly focusing on the physiological costs associated with unnatural light/dark cycles. Birds and mammals offer interesting insights on the role of circadian rhythm disruption due to 1) differences in their ability to receive and relay light information and 2) distinct physiological differences.
Zebra finches (Taeniopygia guttata castanotis) are an opportunistic, diurnal social songbird native to Australia, with well-charactered stress physiology and neurobiology. They are generally insensitive to changes in the photoperiod, meaning that we can disentangle unique physiological responses in response to photoperiod manipulations that mimic human patterns without activating alternate pathways sensitive to photoperiodism associated with life-history transitions. Therefore, zebra finches are the ideal model to evaluate the mechanisms underlying physiological and metabolic effects to altered lighting conditions.
The nocturnal mouse (Mus musculus) has been the prime model to examine the theoretical and mechanistic basis of circadian rhythm biology. Indeed, the ability to easily manipulate their genome to ask targeted questions regarding the pathogenesis of diseases related to circadian rhythm disruption, in combination with other important factors such as diet and exercise has proven extremely useful. Yet, artificial selection may have removed vital components involved in mediating their physiological and behavioral response to stressors, particularly by making strains more docile, and more reproductively capable. Consequently, the genotypes of many lab strains are virtually the same, and common lab rodents used in circadian rhythm research are done in some strains unable to produce melatonin, a key hormone related to biological timekeeping. Thus, studies capitalizing on the wild-derived house mouse that retains natural sensitivity to stressors bridges together the strength of genetic heterogeneity and plasticity, with the utility of controlled laboratory environments to further evaluate nighttime light disturbances on physiology will prove useful.
These ecologically relevant models are at the forefront of my dissertation, in which I explored neuroendocrine, metabolic, and morphological effects of light at night across four data chapters. In chapters 2 and 3, I examined the role of stress resilience by exposing zebra finches to high intensity constant light and allowing a recovery period. I collected samples to address transient and persistent changes in hypothalamic-pituitary-adrenal (HPA) axis and glucose regulation, body mass, and the abundance of glucocorticoid receptors (Chapter 2).
To further evaluate physiological costs to constant light, I investigated the capacity to which zebra finches displayed ephemeral or persistent cellular damage by measuring a suite of damage markers related to DNA, lipids, and proteins across the blood, liver, and skeletal muscle (Chapter 3). To identify the mechanism(s) associated with cellular damage outcomes, I leveraged data collected from Chapter 2 to perform path analysis, synonymous to structural equation modelling (SEM), to reveal how light at night altered the physiological regulatory network after exposure and a recovery period.
In Chapter 4, I investigated the bioenergetic mechanisms related to sex and tissue-specific responses to constant light and darkness in the wild-derived house mouse. While HPA axis function could be a mechanism underlying metabolic or cellular damage outcomes to altered lighting conditions, two alternative mechanisms are declines in mitochondrial respiratory function and resting metabolic rate, both of which, are heavily involved in maintaining metabolic homeostasis and underlie metabolic diseases.
In the last data chapter, to bridge together experimental paradigms and findings from chapters 2-4, I exposed zebra finches to simulated night shift work conditions commonly experienced by human shift workers and experimentally done in rodent models. Here, I extended upon hypothalamic-pituitary-adrenal (HPA) regulation by including negative feedback efficiency, the ability to terminate the adrenocortical response to avoid a long duration of elevated glucocorticoid. Moreover, I evaluated circadian rhythmicity of two key hormones reflective of circadian alignment: corticosterone and melatonin.
In Chapter 2, I found that there were time-dependent effects of constant light on the morphology and physiology of zebra finches in addition to varying degrees of stress resilience. Body mass marginally increased after 3 days of constant light, but after 23 days of exposure to constant light, body mass was significantly higher in treatment birds compared to controls. In contrast, baseline glucose levels decreased over the duration of the experiment, yet these effects were transient, as both body mass and glucose levels rebounded to pretreatment levels after the recovery period, indicating stress resilience. Yet, the glucose stress response was blunted due to constant light, and remained blunted after the recovery period, indicating a persistent effect and a lack of stress resilience. Interestingly, there were no changes in circulating baseline corticosterone, the reactivity of the HPA axis, or the abundance of glucocorticoid receptors in the liver. These data suggest that there is variation in the capacity for different traits to rebound after recovery from a chronic stressor. Yet, questions remain as to if these trends are the result of prioritization of recovery between different traits or is dependent on the length of the recovery period.
In Chapter 3, there were no transient or persistent effects of constant light on global DNA damage in the red blood cells. Furthermore, constant light at night did not result in persistent oxidative damage in the liver or skeletal muscle, measured through protein carbonyls and 4-hydroxynonaneal. However, by leveraging data from chapter 2, a phenotypic integration approach via path analysis revealed interesting associations between traits and their relationship with damage outcomes that were dependent on treatment groups. In control birds, path analysis revealed that HPA axis function was a condition-dependent trait, such that individuals with greater body mass mounted stronger stress responses. Moreover, birds that mounted stronger HPA axis responses also had stronger downstream glucose responses. However, exposure to constant light uncoupled condition-dependency of the stress phenotype, such that after a recovery period, birds previously exposed to light at night had no relationship between body mass, HPA axis function, and the glucose stress response. These data suggest that prior stress history (i.e., exposure and recovery from light at night) may have persistent effects by modifying physiological network linkage between traits within the physiological regulatory network which may underlie damage outcomes.
In Chapter 4, there was a sex and tissue-specific response relating to constant light, but not constant darkness. Specifically, state 3 maximum mitochondrial respiratory function was higher in the liver of female mice exposed to constant light, compared to controls and females under constant darkness. There was not a similar trend in the mitochondrial respiratory response in the male livers, or the skeletal muscles of either sex. While females had greater mitochondrial respiratory function, they did not suffer from greater lipid peroxidation in the liver, indicating that the common assumption between enhanced oxidative phosphorylation capacity and cellular damage is not supported. There were no significant changes in body mass, fat pads, or the resting metabolic rates of mice under constant light or darkness. These data contrast many studies that investigate the effects of light at night in laboratory rodents, emphasizing the importance of individual variation and plasticity. Furthermore, these data highlight that the bioenergetic underpinning of metabolism could improve upon our understanding of metabolic disease to circadian disruption.
In Chapter 5, I found that 24-h corticosterone profiles were inverted an inversion of corticosterone profiles after 63 days of simulated night shift work. There was a similar trend suggesting inversion of melatonin profiles, however, lack of biological samples and statistical power inhibited my ability to capture this effect. I also found that simulated night shift work suppressed HPA axis reactivity, but not negative feedback efficiency. Moreover, simulated night shift work enhanced fatty acid metabolism, indicated by greater number of circulating β-hydroxybutyrate, yet this did not result in changes to body mass or subcutaneous fat deposits. There were no differences in superoxide dismutase 1 or abundance of 4-hydroxynonaneal adducts in the liver. In contrast, there were lower amounts of relative protein abundance of superoxide dismutase 1 in the brain, but no difference between groups in 4-hydroxynonaneal damage in the brain. Overall, the data gathered here indicate plasticity in circadian mechanisms in response to alternating patterns of light at night that mimic night shift work in humans. Such plasticity was able to alleviate some of the physiological costs to simulated night shift work, indicating resilience to alternating patterns of light. | en_US |
