| Research Abstract |
Accumulating lines of evidence indicated that activated microglia exhibit proliferation, morphological changes, phagocytosis and release of bioactive factors, suggesting that the cells play important roles in tissue repair and neural regeneration. Recently we have shown that extracellular ATP activates microglia through various types of ATP receptors. For example, ATP stimulated the release of neuroprotective factors, such as plasminogen, IL-1b, TNF-a and IL-6 by means of ionotropic and metabotropic ATP receptors. We have also shown that ATP and ADP induced membrane ruffling and chemotaxis of cultured microglia. These phenomena were inhibited by pertusis toxin (PTX) and AR-C69931MX, a selective antagonist against of P2Y12 receptor. We examined expression of P2Y12 in adult rat brains using in situ hybridization. P2Y12-expressing cells showed small cell bodies and distributed throughout the brain. The cells increased in the facial nucleus following axotomy, and expressed microglia-specific protein Iba1, indicating that P2Y12-expressing cells in the brain are microglia. We further showed that the small G-protein Rac was activated in microglia by ATP stimulus, and its activation was inhibited by pretreatment with PTX. Iba1, which has been reported to participate specifically in Rac signaling in microglia, was accumulated in membrane ruffles and was phosphorylated under the stimulus of ATP. These findings suggest that Iba1 and Rac are involved in the signaling downstream of P2Y12 receptor during microglial activation.
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