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小胶质细胞利用一系列膜受体来感知周围环境.虽然已知P2Y12受体在小胶质细胞的突起向释放ATP/ADP的损伤部位的靶向运动定中起关键作用,但对P2Y13的作用知之甚少.转录组数据表明P2Y13是小胶质细胞中第2高表达的神经递质受体.本研究显示,在缺乏P2Y13受体小鼠的急性脑切片,膜片钳记录由ADP激活P2Y12受体引起的THIK-1 K +电流密度增加了约50%.这种增加表明P2Y12依赖的趋化性反应增强.但是在P2Y13敲除小鼠,P2Y12介导的小胶质细胞突起向充灌ADP的电极或激光融蚀点聚集所需的时间更长.解剖分析表明,在P2Y13敲除小鼠中,小胶质细胞的密度没有变化,但分枝较少,突起长度较短.因此在基因敲除的小鼠,小胶质细胞趋化的突起必须进一步生长然后才能到达靶标,且脑部监视降低了约30%.在P2Y13敲除小鼠脑片中,阻断P2Y12受体并不会影响监视,表明监视过程不需要这些高亲和力受体的补充激活.令人惊讶的是,在P2Y13敲除小鼠白细胞介素-1β释放的基础值增加了5倍,而LPS和ATP引起的释放不受影响;P2Y13敲除小鼠完整脑中的小胶质细胞未被检测到激活.因此,尽管P2Y13受体与P2Y12非常接近,但它们在调节小胶质细胞形态和功能方面起着不同的作用.“,”Microglia sense their environment using an array of membrane receptors. While P2Y12 receptors are known to play a key role in targeting directed motility of microglial processes to sites of damage where ATP/ADP is released, little is known about the role of P2Y13, which transcriptome data suggest is the second most expressed neu-rotransmitter receptor in microglia. We show that, in patch-clamp recordings in acute brain slices from mice lacking P2Y13 receptors, the THIK-1 K+current density evoked by ADP activating P2Y12 receptors was increased by~50%. This increase suggested that the P2Y12-dependent chemotaxis response should be potentiated; however, the time needed for P2Y12-mediated convergence of microglial processes onto an ADP-filled pipette or to a laser ablation was longer in the P2Y13 KO. Anatomical analysis showed that the density of microglia was unchanged, but that they were less ramified with a shorter process length in the P2Y13 KO. Thus, chemotactic processes had to grow further and so arrived later at the target, and brain surveillance was reduced by~30% in the knock-out. Blocking P2Y12 re-ceptors in brain slices from P2Y13 KO mice did not affect surveillance, demonstrating that tonic activation of these high-affinity receptors is not needed for surveillance. Strikingly, baseline interleukin-1β release was increased five-fold while release evoked by LPS and ATP was not affected in the P2Y13 KO, and microglia in intact P2Y13 KO brains were not detectably activated. Thus, P2Y13 receptors play a role different from that of their close relative P2Y12 in regulating microglial morphology and function.