Department of Neurosurgery, Yongchuan Hospital, Chongqing Medical University, Chongqing, China.
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Brain Behav. 2020 Sep;10(9):e01777. doi: 10.1002/brb3.1777. Epub 2020 Aug 5.
To investigate the effect of estrogen on axon regeneration and neurological recovery after subcortical axon injury, and further explore its underlying molecular mechanisms.
Subcortical axonal fiber injury model was used in this study. Morris water maze was conducted to detect the learning and memory ability of the rats; modified neurological severity score (mNSS) and beam walking test were performed to evaluate the behavioral; and diffusion tensor imaging (DTI) was used for the determination of recovery after subcortical axonal injury, while Western blotting was performed to detect the expression of p-Akt, CDK5, p-Ser262, p-Ser404, and p-Thr205.
Compared with the Sham group, the injury of subcortical axonal fiber resulted in higher mNSS, higher beam walking scores, longer time of escape latency, less number, time and shorter distance of crossing the quadrant, and less FA values. After ovariectomy, the mNSS, beam walking scores, and escape latency reached the peak; inversely, the others reached a minimum. High estrogen treatment reduced the mNSS, beam walking score, and escape latency; improved the number, time, and distance of crossing the quadrant; and increased the FA value. Western blotting results showed that estrogen increased the expression of p-Akt and decreased the expression of CDK5, p-Ser262, p-Ser404, and p-Thr205. All the changes were counteracted to some extent by Akt inhibitor LY294002.
After subcortical axonal injury, estrogen could improve the regeneration of axons and improve their functions via regulating the PI3K/Akt/CDK5/Tau pathway.
探讨雌激素对皮质下轴突损伤后轴突再生和神经功能恢复的影响，并进一步探讨其潜在的分子机制。
本研究采用皮质下轴突纤维损伤模型。通过 Morris 水迷宫检测大鼠的学习记忆能力；改良神经功能严重程度评分（mNSS）和束状行走试验评估行为；扩散张量成像（DTI）用于评估皮质下轴突损伤后的恢复情况，Western blot 检测 p-Akt、CDK5、p-Ser262、p-Ser404 和 p-Thr205 的表达。
与 Sham 组相比，皮质下轴突纤维损伤导致 mNSS 升高、束状行走评分升高、逃避潜伏期延长、穿越象限的次数、时间和距离减少，FA 值降低。卵巢切除后，mNSS、束状行走评分和逃避潜伏期达到峰值；相反，其他指标达到最低。高雌激素处理降低了 mNSS、束状行走评分和逃避潜伏期；增加了穿越象限的次数、时间和距离；并增加了 FA 值。Western blot 结果表明，雌激素增加了 p-Akt 的表达，降低了 CDK5、p-Ser262、p-Ser404 和 p-Thr205 的表达。Akt 抑制剂 LY294002 部分拮抗了这些变化。
皮质下轴突损伤后，雌激素通过调节 PI3K/Akt/CDK5/Tau 通路，促进轴突再生，改善其功能。
