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Projekt
The interplay between P2 and P1 receptors to control microglial function
Antragsteller
Professor Dr. Helmut Kettenmann
Fachliche Zuordnung
Klinische Neurologie; Neurochirurgie und Neuroradiologie
Förderung
Förderung von 2007 bis 2015
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 22935240
Microglial cells are the pathologic sensors in the CNS and migrate to the site of injury, phagocytose, and release a variety of factors like cytokines, chemokines, nitric oxide and growth factors. Our project focuses on the interplay between P2 and P1 receptors to control microglial functions. In the brain extracellular space, ATP is rapidly degraded and, two prominent ectonucleotidases, cd39 degrading ATP to AMP and cd73 degrading AMP into adenosine, are exclusively expressed by microglial cells. By using mice with genetic deletions of these enzymes we plan to determine how the interplay between these two receptor systems determines microglial function. We have recent evidence that microglial migration is controled by co-activation of P2 and P1 receptors. We plan to study how other important microglial functions are controled by combined activation of these receptors. Of particular interest is the release of cytokines where purinergic receptors play a dual role, triggering a rapid release, but also attenuating long-term release in the context of microglial activation. Moreover, recent evidence indicates that the P2/P1 receptor system is additionally modulated by other receptors namely serotonin and dopamine.
DFG-Verfahren
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