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For more than 3 billion years, life outside the highest latitudes has evolved under brightly illuminated days and dark nights. Most organisms have developed endogenously driven circadian rhythms which are synchronized to this light/dark cycle. In recent years, daily light schedules have become artificial and irregular due to the use of electric lighting. In this dissertation, I propose that exposure to light at night (LAN) disrupts the circadian system altering metabolic, immunological, and behavioral functions. The global increase in the prevalence of obesity and metabolic disorders coincides with increases in exposure to LAN and shift work. Therefore, my first experiments examined whether exposure to LAN affects metabolism. Mice exposed to dimly lit (5 lux) as compared to dark nights increased body mass and reduced glucose processing without changing caloric intake or activity. Exposure to dim light at night diminished the daily rhythm in food intake and restricting food access to the dark phase prevented weight gain in mice exposed to dimly lit nights (Chapter 2). Furthermore, metabolic changes associated with exposure to LAN are not permanent; placing mice back in dark nights partially reversed increases in body mass caused by exposure to dim light at night (Chapter 3). In Chapters 4 & 5, I investigated the interactions among LAN and more traditional risk factors for obesity such as high fat diet and lethargy. Because light is the most potent synchronizing factor for the circadian system and disruption in clock genes is associated with significant changes in metabolism, I next investigated the effects of exposure to LAN on the circadian system (Chapter 6). Exposure to dimly lit nights attenuated core circadian clock rhythms in both the master circadian pacemaker and peripheral tissues. In addition to altering metabolism, exposure to LAN is implicated as a contributing factor to several diseases involving dysregulation of the immune system. This led to experiments examining the effects of acute exposure to dim LAN on recovery following cardiac arrest (Chapter 7). Exposure to dimly lit as compared to dark nights following global ischemia increased hippocampal inflammation, neuronal cell death, and mortality. Selectively inhibiting inflammation and altering the spectrum of nighttime light to which mice were exposed reduced damage among mice exposed to dim LAN. In the experiments described above, I worked with nocturnal mice in order to assess the effects of nighttime light exposure independent of changes in sleep architecture. However, the secretion patterns of many hormones and immune parameters are different in nocturnal and diurnal species. In the final set of experiments, I demonstrated that diurnal Nile Grass rats (Arvicanthus Niloticus) exposed to dim LAN increased immunological measures (Chapter 8) and altered hippocampal connectivity in addition to changing cognitive and affective behaviors (Chapter 9). Taken together, these studies indicate that exposure to ecologically relevant levels of dim LAN attenuate core circadian clock mechanisms in rodents resulting in physiological and behavioral consequences. |
