Abstract：
Spinal cord injury (SCI) can cause secondary brain changes, leading to hypomyelination in the dorsolateral prefrontal cortex (dlPFC). Some studies have shown that notch signaling pathway activation can regulate oligodendrocyte maturation and myelination. The aim of this study was to investigate whether inhibition of the Notch signaling pathway can alleviate hypomyelination in the dlPFC caused by SCI. Moreover, we further investigated whether the changes in myelination in the dlPFC are associated with neuropathic pain following SCI. We established a mouse model of SCI and observed the changes in mechanical and thermal hyperalgesia. Western blotting and immunofluorescence were used to analyze the changes in myelination in the dlPFC. The results indicated the existence of a relationship between activation of the Notch signaling pathway and hypomyelination in the dlPFC and confirmed the existence of a relationship between hypomyelination in the dlPFC and decreases in mechanical and thermal hyperalgesia thresholds. In conclusion, these results suggested that the Notch signaling pathway is activated after SCI, leading to hypomyelination in the dlPFC, and that DAPT can inhibit the Notch signaling pathway and improve mechanical and thermal hyperalgesia thresholds. Our findings provide a new target for the treatment of neuropathic pain caused by SCI.
摘要：
脊髓损伤（SCI）可引起继发性脑改变，导致背外侧前额叶皮层（dlPFC）的脊髓过度分裂。一些研究表明，Notch信号通路的激活可以调节少突胶质细胞的成熟和髓鞘形成。这项研究的目的是研究Notch信号通路的抑制是否可以减轻SCI引起的dlPFC中的骨髓增生过少。此外，我们进一步调查了dlPFC中髓鞘形成的变化是否与SCI后的神经性疼痛相关.我们建立了SCI小鼠模型，观察了机械和热痛觉过敏的变化。使用Western印迹和免疫荧光分析dlPFC中髓鞘形成的变化。结果表明dlPFC中Notch信号通路的激活与髓鞘减少之间存在关系，并证实dlPFC中髓鞘减少与机械和热痛觉过敏阈值降低之间存在关系。总之,这些结果表明，Notch信号通路在SCI后被激活，导致dlPFC中的髓鞘减少，DAPT可以抑制Notch信号通路，提高机械和热痛觉过敏阈值。我们的发现为SCI引起的神经病理性疼痛的治疗提供了新的靶点。
