UCR Division of Biomedical Sciences

Associate Professor Biomedical Sciences

Ph.D., University of Pennsylvania

Research Summary:

The role of microglia in the central nervous system (CNS)

Microglia are the tissue macrophage of the brain and spinal cord. Their activation is among the earliest responses to almost any change in CNS physiology. Found scattered throughout all regions of the CNS, microglia are strategically located to regulate the onset, progression and termination of CNS inflammatory responses.

We are taking two different approaches to define the relative contributions of microglia toward neuroprotection and neurodegeneration. First, we are examining how microglia and T cells cross-regulate microglial activation and T cell effector function by antigen-dependent and independent mechanisms using transgenic mouse models of CNS inflammation and neurodegeneration. Second, we have profiled a broad array of microglial expressed genes as a function of age, brain region and health status to define microglial phenotype and function in vivo on a molecular level. Using these molecular criteria, we detect multiple subsets of microglia in the healthy unmanipulated CNS. In addition, we find that these phenotypes slowly change during development and as a function of extreme age. We are currently examining the roles of these microglial subsets in the healthy and inflamed CNS, contrasting normal murine CNS development with defined pathologies in murine models of CNS autoimmunity and Alzheimer’s disease.

In aggregate our studies demonstrate that:

1) Microglia are a CNS-specific type of tissue macrophage that differ from inflammatory macrophages that acutely infiltrate the CNS.

2) Microglia interactions with the immune system can actually be beneficial for the CNS.

3) Microglia display stable heterogeneity in the healthy adult CNS, perhaps reflecting the different needs of the diverse neuronal populations they defend and support.

4) Microglial activation is not merely on versus off. Rather, activation is exquisitely tailored to CNS region and to the activating stimulus.

5) CNS inflammatory responses to identical stimuli are likely to change as a function of age-related changes in microglial phenotype.

Selected Recent Publications:

Papenfuss, T.L., Thrash, J.C., Danielson, P.E., Foye, P.E., Hllbrush, B.S., Sutcliffe, J.G., Whitacre, C.C. and Carson, M.J. Induction of golli-MBP expression in CNS macrophages during acute LPS-induced CNS inflammation and experimental autoimmune encephalomyelitis (EAE). The Scientific World Journal 7: 112-120, 2007.

Plant, S.R., Iocca, H.A., Wang, Y., Thrash, J.C., O'Connor, B.P., Arnett, H.A., Fu, Y.X., Carson, M.J. and Ting, J.P. Lymphotoxin beta receptor (Lt betaR): dual roles in demyelination and remyelination and successful therapeutic intervention using Lt betaR-Ig protein. J. Neurosci. 27: 7429-7437, 2007.

Lee, J.W., Bajwa, P.J., Carson, M.J., Jeske, D.R., Cong, Y., Elson, C.O., Lytle, C., and Straus, D.S. Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice. Gastroenterology 133: 108-123, 2007.

Carson, M.J., Bilousova, T.V., Puntambekar, S.S., Melchoir, B., Doose, J.M. and Ethell, I.M. A rose by any other name?: The potential consequences of microglial heterogeneity during CNS health and disease. Neurotherapeutics 4: 571-579, 2007.

Carson, M.J. and Lo, D.D. Perspective is everything: an irreverent discussion of CNS-immune system interactions as viewed from different scientific traditions. Brain Behav. Immun. 21: 367-373, 2007.

Carson, M.J., Doose, J.M., Melchior, B., Schmid, C.D. and Ploix, C.C. CNS immune privilege: hiding in plain sight. Immunol. Rev. 213:48-65, 2006.

Vemuganti, R. and Carson, M.J. Cerebral inflammation: How homeland defense is handled in the CNS. Neurochemistry International 49:1-2, 2006.

MONICA CARSON, PH.D.