Slit2/Robo1 Mediation of Synaptic Plasticity Contributes to Bone Cancer Pain

详细信息    查看全文

• 作者：Changbin Ke ; Feng Gao ; Xuebi Tian ; Caijuan Li ; Dai Shi…
• 关键词：Bone cancer pain ; Spinal cord ; Synaptic plasticity ; Slit ; Roundabout ; Neurite outgrowth
• 刊名：Molecular Neurobiology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：54
• 期：1
• 页码：295-307
• 全文大小：
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182
• 卷排序：54

文摘

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.