The Fonken lab investigates neuroimmune interactions during brain development and aging, with a focus on behavioral outcomes. We are particularly interested in how environmental perturbations alter the function of microglia, key innate immune cells of the central nervous system. We currently have two main research directions.
Project 1. Targeting neuroinflammatory responses in the aged brain to improve cognitive function. We are exploring how to promote effective microglial responses in the aged brain. Over the course of an animal’s lifespan, microglia tend to become more reactive or ‘primed’. This can worsen pathological outcomes when aged animals encounter immune challenges (e.g. infection, surgery, or injury). We are investigating mechanisms that underlie microglia priming with age, and are exploring strategies to dampen priming of aged microglia. In particular, in modern society, unusually sterile conditions may worsen neuroinflammation. The “old friends” hypothesis states that the immune system co-evolved with microorganisms that help program immunity during development, and that underexposure to these organisms can harm immune function. Reintroduction of microorganisms in a “clean” environment can improve the composition of the microbiome and quell hyperactive inflammatory responses. Despite the therapeutic potential of specific small microbes, few studies have assessed whether the immunoregulatory benefits of microbial based treatments target the central nervous system. Here we will investigate the mechanisms by which vaccination with a widely distributed soil bacterium, Mycobacterium vaccae (M. vaccae; NCTC11659), prevents exacerbated neuroinflammatory and behavioral deficits in aging.
Project 2. Circadian regulation of neuroimmune function. We aim to understand how the circadian system regulates neuroinflammatory function. In Dr. Fonken’s postdoctoral research, she established that microglia express circadian timekeeping mechanisms which can gate the inflammatory response. Current projects will reveal the timing of circadian development in microglia and how developmental disruptions of the circadian system affect neuroimmune function.
Selected publications (Full list)
Fonken, L.K., Frank, M.G., D’Angelo, H.M., Heinze, J.D., Watkins, L.R., Lowry, C.A., & Maier, S.F. (2018). Mycobacterium vaccaeimmunization protects aged rats from surgery-elicited neuroinflammation and cognitive dysfunction. Neurobiology of Aging: In press.
Fonken, L.K., Frank, M.G., Kitt, M.M., D’Angelo, H.M., Norden, D.M., Weber, M.D., Barrientos, R.M., Godbout, J.P., Watkins, L.R., & Maier, S.M. (2016). The alarmin HMGB1 mediates age-induced neuroinflammatory priming. The Journal of Neuroscience 36 (30): 7946-7956.
Fonken, L.K., Frank, M.G., Kitt, M.M., Barrientos, R.M., Watkins, L.R., & Maier, S.F. (2015). Microglia inflammatory responses are controlled by an intrinsic circadian clock. Brain, Behavior, and Immunity 45: 171-179.
Fonken, L.K., Xu, X., Weil, Z.M., Chen, G., Sun, Q., Rajagopalan, S., & Nelson, R.J. (2011). Air pollution impairs cognition, provokes depressive-like behaviors, and alters hippocampal cytokine expression and morphology. Molecular Psychiatry. 16 (10): 987-995.
Fonken, L.K., Workman, J.L., Walton, J.C., Weil, Z.M., Morris, J.S., Haim, A., & Nelson, R.J. (2010). Light at night increases body mass by shifting the time of food intake. Proceedings of the National Academy of Sciences, 107 (43): 18664-18669.