Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain.
Microglial P2Y12 receptors regulate microglial activation and surveillance during neuropathic pain.
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小胶质细胞 P2Y12 受体调节神经病理性疼痛期间小胶质细胞的激活和监测
DOI：
10.1016/j.bbi.2015.11.007
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发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Wu LJ
中科院分区：
文献类型：
--
作者：
Gu N;Eyo UB;Murugan M;Peng J;Matta S;Dong H;Wu LJ
小胶质细胞在神经病理性疼痛的发病机制中至关重要，并且已经提出了几种小胶质细胞受体来介导这一过程。在这些受体中，P2 Y12受体是一种独特的嘌呤能受体，其仅由中枢神经系统（CNS）中的小胶质细胞表达。在这项研究中，我们着手调查的作用P2 Y12受体在小胶质细胞的电生理和形态（静态和动态）激活脊髓神经横断（SNT）诱导的神经病理性疼痛小鼠。首先，我们发现P2 Y12受体的遗传缺陷（P2 Y12 −/−小鼠）在神经性疼痛的起始阶段改善了疼痛超敏反应。接下来，我们的特点是在SNT损伤后的脊髓背角浅层的小胶质细胞的电生理和形态学特性。我们显示了显著的变化，包括在损伤后3天的小胶质细胞电生理学的峰值，而高分辨率双光子成像显示了损伤后7天的静态和动态小胶质细胞形态学特性的显着变化。最后，在P2 Y12 −/−小鼠中，这些电生理和形态学变化得到改善，表明P2 Y12受体在SNT诱导的小胶质细胞活化中的作用。因此，我们的研究结果表明，P2 Y12受体调节小胶质细胞的电生理以及周围神经损伤后的静态和动态小胶质细胞的特性，这表明小胶质细胞P2 Y12受体可能是一个潜在的治疗靶点，用于治疗神经病理性疼痛。
Microglial cells are critical in the pathogenesis of neuropathic pain and several microglial receptors have been proposed to mediate this process. Of these receptors, the P2Y12 receptor is a unique purinergic receptor that is exclusively expressed by microglia in the central nervous system (CNS). In this study, we set forth to investigate the role of P2Y12 receptors in microglial electrophysiological and morphological (static and dynamic) activation during spinal nerve transection (SNT)-induced neuropathic pain in mice. First, we found that a genetic deficiency of the P2Y12 receptor (P2Y12−/− mice) ameliorated pain hypersensitivities during the initiation phase of neuropathic pain. Next, we characterized both the electrophysiological and morphological properties of microglia in the superficial spinal cord dorsal horn following SNT injury. We show dramatic alterations including a peak at 3 days post injury in microglial electrophysiology while high resolution two-photon imaging revealed significant changes of both static and dynamic microglial morphological properties by 7 days post injury. Finally, in P2Y12−/− mice, these electrophysiological and morphological changes were ameliorated suggesting roles for P2Y12 receptors in SNT-induced microglial activation. Our results therefore indicate that P2Y12 receptors regulate microglial electrophysiological as well as static and dynamic microglial properties after peripheral nerve injury, suggesting that the microglial P2Y12 receptor could be a potential therapeutic target for the treatment of neuropathic pain.