GPR17 expression in healthy and injured spinal cord

Acute spinal cord injury (SCI) results in immediate tissue damage, followed by long-lasting secondary injury associated to the release of inflammatory molecules, including nucleotides, which may contribute to damage development by activating specific membrane receptors. In this respect, the pathological over-activation of the new purinergic receptor GPR17 has been recently proposed to participate to brain ischemia (Ciana et al., 2006. EMBO J 25:4615). In this study we aimed at evaluating GPR17 expression in the spinal cord and its possible role in SCI-associated damage. Adult mice were subjected to extradural SCI with an aneurysm clip after T6-T9 laminectomy and injected with bromodeoxyuridine to evaluate cell proliferation. GPR17 expression was evaluated by immunohistochemistry 24h, 72h and 1 week after injury. In sham-operated mice, GPR17 was expressed by many III-tubulin-positive neurons and CC1-positive oligodendrocytes, but not by GFAP-positive astrocytes. Ependymal cells and the 29.8±2.1% of cells expressing the neuroprogenitor marker NG2 also expressed GPR17. After SCI, cell proliferation strongly increased in parallel with the total number of GPR17-expressing cells. In fact, despite the massive death of GPR17-positive neurons and oligodendrocytes, a proliferating population of GPR17- and IB4-positive microglia/macrophages emerged. GPR17 was never found in Nestin- and GFAP double-positive reactive astrocytes. Taken together, in a similar way to brain ischemia, our data show an increase in GPR17 expression that may contribute to acute SCI damage. On the other hand, presence of GPR17 on neuroprogenitor-like cells also suggests a potential role of this receptor in the long-term reparative changes associated to SCI