Daily rhythms in immunity compartmentalize the energetic costs of maintaining immune capacity. The circadian input driving these rhythms is dependent on distinct environmental light/dark signals. Since the turn of the century there has been a widespread adoption of electrical lighting both within and outside the home. Blurring of light/dark signals, through exposure to light at night (LAN), affects metabolic, endocrine, and immune function. LAN alters rhythms in melatonin and glucocorticoids. Melatonin enhances immune function, whereas glucocorticoids have opposing effects in the brain and periphery. Exposure to LAN also dampens response to delayed type hypersensitivity (DTH), an antigen specific T-cell mediated immune response, and increases microglial response to lipopolysaccharide (LPS). Together these results suggest central immune-enhancement and peripheral immunosuppression in animals exposed to dim LAN, akin to the effect of glucocorticoids. However, studies thus far have focused on the relatively immediate effects of LAN and much less on the persisting effects of this systemic disruption. Preliminary results indicate that offspring whose parents were exposed to dim LAN for 8 weeks prior to mating have dampened DTH responses. Specifically, maternal exposure to dim LAN compromises male offspring DTH responses, whereas female offspring DTH response is affected by paternal lighting condition. In the proposed project I will investigate the role of parental LAN exposure on offspring fitness, proxied by immune function and attractiveness. Offspring immune function will be assessed by testing B cell, T cell, and macrophage/microglial responses to keyhole limpet hemocyanin (KLH), dinitrofluorobenzene (DNFB), and lipopolyssacharide (LPS), respectively. Attractiveness will be assessed in both sexes using a three-chamber social preference test. Finally, I will investigate epigenetic changes in melatonin (MT1) and glucocorticoid (GR) receptor expression in the brain and immune tissues as a mediator for impaired immune function in offspring. Hypothesis: Melatonin and cortisol are highly circadian rhythmic and have opposing immunomodulatory roles. Disruption of distinct light/dark signals, through LAN exposure, impairs rhythmic hormone expression and immune function. We hypothesize that circadian disruption through dim LAN exposure in parents will affect offspring immune function and attractiveness through epigenetic changes in MT1 and GR expression in the brain and immune tissues.
Aim 1. To determine whether parental exposure to LAN has functional consequences in terms of offspring immune function.
Aim 2. To determine whether parental exposure to LAN has functional consequences in terms of offspring reproductive success.
Aim 3. To investigate epigenetic modifications to melatonin and glucocorticoid receptor expression in the brain and immune tissues as mediators for altered immune function.
Circadian disruption, through exposure to light at night (LAN), impairs immune function as well as the rhythmic release of melatonin and glucocorticoids. This project will investigate the role of parental LAN exposure, as an endocrine disruptor, on offspring immune function. Results from this study will outline the transgenerational health consequences of a seemingly innocuous environmental pollutant, LAN.
| Cissé, Yasmine M; Borniger, Jeremy C; Lemanski, Elise et al. (2018) Time-Restricted Feeding Alters the Innate Immune Response to Bacterial Endotoxin. J Immunol 200:681-687 |
| Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J (2017) Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity. Sci Rep 7:45497 |
| Cissé, Yasmine M; Russart, Kathryn L G; Nelson, Randy J (2017) Depressive-like behavior is elevated among offspring of parents exposed to dim light at night prior to mating. Psychoneuroendocrinology 83:182-186 |
