Project Details
Projekt
The interplay between P2 and P1 receptors to control microglial function
Applicant
Professor Dr. Helmut Kettenmann
Subject Area
Clinical Neurology; Neurosurgery and Neuroradiology
Term
from 2007 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme
Research Units
