Slit2/Robo1 Mediation of Synaptic Plasticity Contributes to Bone Cancer Pain
Slit2/Robo1 Mediation of Synaptic Plasticity Contributes to Bone Cancer Pain
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DOI：
10.1007/s12035-015-9564-9
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发表时间：
2017-01-01
影响因子：
5.1
通讯作者：
Tian, Yuke
中科院分区：
文献类型：
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作者：
Ke, Changbin;Gao, Feng;Tian, Yuke
突触的可塑性是脊椎对骨癌疼痛敏感的基础。在这里，我们已经证明了兴奋性突触发生与骨癌疼痛有关。新的突触形成需要轴突生长和轴突与树突之间的相互作用，伴随着突触前和突触后特化的同位组织。我们已经证明Slit2、Robo1和RhoA作为这样的信号促进轴突生长并引导轴突形成突触。肉瘤接种可诱导兴奋性突触形成和骨癌疼痛，Slit2基因敲除可逆转这些作用，而Robo1基因敲除则加重这些效应。Slit2基因敲除抑制了培养神经元的突触发生，而Robo1基因敲除则促进了突触发生。肉瘤种植导致Slit2增加，Robo1和RhoA减少，而Slit2基因敲除导致Robo1和RhoA增加。这些结果证实了骨癌痛中突触发生的分子机制。
Synaptic plasticity is fundamental to spinal sensitivity of bone cancer pain. Here, we have shown that excitatory synaptogenesis contributes to bone cancer pain. New synapse formation requires neurite outgrowth and an interaction between axons and dendrites, accompanied by the appositional organization of presynaptic and postsynaptic specializations. We have shown that Slit2, Robo1, and RhoA act as such cues that promote neurite outgrowth and guide the axon for synapse formation. Sarcoma inoculation induces excitatory synaptogenesis and bone cancer pain which are reversed by Slit2 knockdown but aggravated by Robo1 knockdown. Synaptogenesis of cultured neurons are inhibited by Slit2 knockdown but enhanced by Robo1 knockdown. Sarcoma implantation induces an increase in Slit2 and decreases Robo1 and RhoA, while Slit2 knockdown results in an increase of Robo1 and RhoA. These results have demonstrated a molecular mechanism of synaptogenesis in bone cancer pain.