OF PROPOSED ADMINISTRATIVE SUPPLEMENT. We are requesting a one-year Alzheimer's-focused administrative supplement for grant RO1-NS 92388 (Notice Number: NOT- AG-18-039). In the course of our work on cardiac arrest outcomes, we have discovered that several features of the brain vasculature are altered by exposure to dim light at night, and that the changes occur rapidly. For example, in otherwise healthy, young adult mice as little as four nights of exposure to dim light at night (5 lux) causes a reduction in hippocampal blood vessels. Likewise, markers of angiogenesis (e.g., VEGF) are also reduced. Based on these observations, we hypothesize that exposure to light at night may promote vascular cognitive impairment and dementia (VCID). Indeed, most victims of VCID live in spaces that are illuminated by dim light at night to ensure the safety of the residents and nightshift staff. We believe that circadian disruption caused by light at night promotes the deterioration of the brain vasculature, resulting in cognitive impairments. To test this hypothesis, we plan to expose aged (72 week old) male and female mice to dark nights or dim light at night, then after 1 versus 8 weeks of the lighting condition we will commence cognitive testing. At these time points, brain vasculature, markers of angiogenesis, and neuroinflammation will be assessed in a separate cohort of mice. In addition, we will include experimental groups in which mice are exposed to a restricted spectrum of dim blue or dim red light at night (equalized for lux and photic energy). We predict that mice exposed to dim blue and or white light at night will display increased neuroinflammation, and cognitive and blood flow impairments relative to mice exposed to dim red light at night or dark nights. This outcome would suggest that restricting the wavelength of nighttime lighting could offer a low-cost, effective means to delay or prevent VCID in elderly individuals. This administrative supplement would allow us to develop a foundation on which to build a full R01 on VCID to understand the mechanisms involved.
Around the clock exposure to light has long been considered an innocuous consequence of industrialization and modernization. To the contrary, there is now accumulating epidemiological data suggesting that exposure to light at night can cause circadian rhythm disruption, which in turn increases an individual?s susceptibility to a wide range of medical conditions from mood disorders to cancer. We propose that exposure to light at night, as often experienced in an extended care setting, also can impair vascular function and repair. Our goal is to use mice to determine how light at night alters vasculature, vascular remodeling, and the neurocognitive and inflammatory outcomes in aged mice as an animal model of vascular cognitive impairment and dementia (VCID).
| Emmer, Kathryn M; Russart, Kathryn L G; Walker, William H et al. (2018) Effects of light at night on laboratory animals and research outcomes. Behav Neurosci 132:302-314 |
| Russart, Kathryn L G; Huk, Danielle; Nelson, Randy J et al. (2018) Elevated aggressive behavior in male mice with thyroid-specific Prkar1a and global Epac1 gene deletion. Horm Behav 98:121-129 |
| Russart, Kathryn L G; Nelson, Randy J (2018) Artificial light at night alters behavior in laboratory and wild animals. J Exp Zool A Ecol Integr Physiol 329:401-408 |
| Nelson, Randy J; Chbeir, Souhad (2018) Dark matters: effects of light at night on metabolism. Proc Nutr Soc 77:223-229 |
| Gaudier-Diaz, Monica M; Haines, Adam H; Zhang, Ning et al. (2018) Social influences on microglial reactivity and neuronal damage after cardiac arrest/cardiopulmonary resuscitation. Physiol Behav 194:437-449 |
| Russart, Kathryn L G; Nelson, Randy J (2018) Light at night as an environmental endocrine disruptor. Physiol Behav 190:82-89 |
| Bedrosian, T A; Nelson, R J (2017) Timing of light exposure affects mood and brain circuits. Transl Psychiatry 7:e1017 |
| Gaudier-Diaz, Monica M; Zhang, Ning; Haines, Adam H et al. (2017) Social interaction modulates the neuroinflammatory response to global cerebral ischemia in male mice. Brain Res 1673:86-94 |
| Dominoni, Davide M; Borniger, Jeremy C; Nelson, Randy J (2016) Light at night, clocks and health: from humans to wild organisms. Biol Lett 12:20160015 |
