Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, NO17 Yong Wai Zheng Street, Nanchang, 330006, Jiangxi, People's Republic of China.
School of Basic Medicine, Jiujiang University, Jiujiang, 332005, Jiangxi, People's Republic of China.
Neurochem Res. 2022 Jun;47(6):1651-1663. doi: 10.1007/s11064-022-03558-4. Epub 2022 Feb 24.
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.
脊髓损伤（SCI）可导致继发性脑改变，导致背外侧前额叶皮质（dlPFC）出现少突胶质细胞发育不全。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。本研究旨在探讨 Notch 信号通路的抑制是否可以减轻 SCI 引起的 dlPFC 少突胶质细胞发育不全。此外，我们还进一步探讨了 dlPFC 中的髓鞘变化是否与 SCI 后的神经病理性疼痛有关。我们建立了 SCI 小鼠模型，并观察了机械性和热痛觉过敏的变化。采用 Western blot 和免疫荧光技术分析 dlPFC 中髓鞘的变化。结果表明 Notch 信号通路的激活与 dlPFC 中的少突胶质细胞发育不全之间存在关系，并证实了 dlPFC 中的少突胶质细胞发育不全与机械性和热痛觉过敏阈值降低之间存在关系。总之，这些结果表明，SCI 后 Notch 信号通路被激活，导致 dlPFC 出现少突胶质细胞发育不全，DAPT 可抑制 Notch 信号通路，改善机械性和热痛觉过敏阈值。我们的研究结果为治疗 SCI 引起的神经病理性疼痛提供了新的靶点。
