Involvement of P2X and P2Y receptors in microglial activation in vivo |
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Authors: | H Franke C Schepper P Illes U Krügel |
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Institution: | Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstr. 16–18, D-04107 Leipzig, Germany |
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Abstract: | Microglial cells are the primary immune effector cells in the brain. Extracellular ATP, e.g., released after brain injury,
may initiate microglial activation via stimulation of purinergic receptors. In the rat nucleus accumbens (NAc), the involvement
of P2X and P2Y receptors in the generation of microglial reaction in vivo was investigated. A stab wound in the NAc increased
immunoreactivity (IR) for P2X1,2,4,7 and P2Y1,2,4,6,12 receptors on microglial cells when visualized with confocal laser scanning microscopy. A prominent immunolabeling of P2X7 receptors with antibodies directed against the ecto- or endodomain was found on Griffonia simplicifolia isolectin-B4-positive cells. Additionally, the P2X7 receptor was colocalized with active caspase 3 but not with the anti-apoptotic marker pAkt. Four days after local application
of the agonists α,βmeATP, ADPβS, 2MeSATP, and BzATP, an increase in OX 42- and G. simplicifolia isolectin-IR was observed around the stab wound, quantified both densitometrically and by counting the number of ramified
and activated microglial cells, whereas UTPγS appeared to be ineffective. The P2 receptor antagonists PPADS and BBG decreased
the injury-induced increase of these IRs when given alone and in addition inhibited the agonist effects. Further, the intra-accumbally
applied P2X7 receptor agonist BzATP induced an increase in the number of caspase-3-positive cells. These results indicate that ATP, acting
via different P2X and P2Y receptors, is a signaling molecule in microglial cell activation after injury in vivo. The up-regulation
of P2X7-IR after injury suggests that this receptor is involved in apoptotic rather than proliferative effects. |
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Keywords: | CNS Injury Microglia P2 receptors Trauma |
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