SCoBIRC FACULTY

Annadora J. Bruce-Keller, Ph.D.

Associate Professor,
Department of Anatomy & Neurobiology

University of Southern California (1995)
Postdoctoral training at University of Kentucky

Research Interests

Hormones, Immunology and the Brain

Why are women more likely then men to develop Alzheimer's disease in later life? Why do more women then men suffer from autoimmune disorders?

The answers to these questions lie buried in complex interactions between the endocrine system, immune system, and the nervous system. In the broadest sense, our lab is studying these interactions, with specific emphasis on the effects of estrogen on immune and neuro-immune function. For instance, we have determined that physiological doses of estrogen can decrease microglial activation. This observation may have important ramifications for age-related neuro-immune disorders, such as Alzheimer's disease. As the principle brain-resident immunocompetent cell, microglial cells have an elaborate repertoire of cellular responses to defend the brain from external threats, including the ability to secrete low-molecular weight neurotoxins, free radicals, and complement factors; as well as the ability to phagocytize foreign bodies and damaged tissue. However, based on the extreme cytotoxic potential of these neuro-inflammatory pathways, it can proposed that prolonged microglial activation in the brain contributes to (if not carries) brain injury, and should be pharmacologically abated. Hence, plummeting estrogen levels in post-menopausal women may be a factor in the development of AD by allowing for unchecked microglial activation. This association between estrogen and microglial activation may partially explain why both estrogen replacement therapy and long-term anti-inflammatory drug therapy decreases a women's risk for AD.

Additionally, estrogen has extremely potent effects on the immune system, as evidencedby both the increased prevalence of autoimmune disorders in women and in the alterations in humoral immunity during pregnancy. We have recently become very interested in the role that female steroid hormones play in the physiological control of the immune system, and specifically how estrogen could play into such immunological disorders as Multiple Sclerosis and HIV.

Select Publications

Bruce, A.J., W.W. Boling, J. Keller, M. Kindy, J. Peschon and M.P. Mattson (1996) Altered responses to ischemic and excitotoxic brain injury in transgenic mice lacking tumor necrosis factor receptors. Nature Medicine. 2: 788-794.

Bruce-Keller, A.J. and M.P. Mattson (1998) Modulatory role of NFkB in neuronal and glial responses to injury. In (J. Kreiglestein, Ed) “Proceedings of the 6th International Symposium on the Pharmacology of Cerebral Ischemia” MedPharm Pub, Inc., Stuttgart, 309-317.

Bruce-Keller, A.J., J.W. Geddes, P.E. Knapp, R.W. McFall, J.N. Keller, S. Parthanathy, S. Steiner, and M.P. Mattson (1999) Anti-death properties of TNF against metabolic poisoning: mitochondrial stabilization by MnSOD. J. Neuroimmunol. 93:53-71.

Bruce-Keller, A.J. R.W. McFall, G.H. Umberger, and M.P. Mattson (1999) Caloric restriction decreases neuronal vulnerability to excitotoxic and metabolic injury. Ann. Neurol. 45: 8-15.

Bruce-Keller, A.J. (1999) Microglial - neuronal signaling and synaptic damage and recovery. In (M.P. Mattson, D. Alkon, and A.J. Bruce-Keller, Eds) “Synaptic Signaling in Plasticity and Apoptosis” Journal of Neuroscience Research, In Press.

Bruce-Keller, A.J., J.L. Keeling, J.N. Keller, F.F. Huang, S. Camondola, and M.P. Mattson (2000) Anti-inflammatory properties of estrogen on microglial activation. Endocrinology 141: 3646-3656.

Bruce-Keller, A.J., S.W. Barger, N. Moss, J. Pham, J.N. Keller, and A. Nath (2001) Pro-inflammatory and pro-oxidant properties of the HIV protein Tat in microglia: attenuation by 17b-estradiol. J. Neurochem. J. Neurochem. 78: 1315-1324, 2001.

Bruce-Keller, A.J. and Estus, S. Concern over the amyloid vaccine: amyloid heterogeneity and Fc receptor signaling. Neurobiology of Aging 23: 677-678, 2002.