Identification of a novel regulatory mechanism to suppress cellular activation in the brain.

Many neurological diseases are characterized by the activation of resident brain cells. In particular microglia, macrophage-like cells of the central nervous system, are thought to have important roles during the immunopathology of diseases as multiple sclerosis and Alheimer’s disease.

Biomedical research into central nervous system diseases using experimental animals is often seriously discomforting. Within the Alternatives Unit we have therefore setup in vitro cell culture systems that are initiated from material that becomes available when animals are euthanized for other purposes. Using such a culture system for microglia we have identified a novel regulatory mechanism in microglia. When microglia were activated by exposure to e.g. viral antigens, they altered their profile of cell surface receptor proteins. This altered profile rendered microglia much more sensitive to suppressive signaling and might represent a natural break to prevent overactivation. Future research might make it possible to exploit this mechanism for therapeutical purposes.

van der Putten C, Zuiderwijk-Sick EA, van Straalen L, de Geus ED, Boven LA, Kondova I, IJzerman AP, Bajramovic JJ. Differential expression of adenosine A3 receptors controls adenosine A2A receptor-mediated inhibition of TLR responses in microglia. J Immunol. 2009 Jun 15;182(12):7603-12.

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