SVCT2 Promotes Neural Stem/Progenitor Cells Migration Through Activating CDC42 After Ischemic Stroke
SVCT2 Promotes Neural Stem/Progenitor Cells Migration Through Activating CDC42 After Ischemic Stroke
复制标题
缺血性中风后 SVCT2 通过激活 CDC42 促进神经干/祖细胞迁移
DOI：
10.3389/fncel.2019.00429
复制
发表时间：
2019-09
期刊：
影响因子：
--
通讯作者：
Feng H.
中科院分区：
文献类型：
--
作者：
Yang Y;Zhang K;Chen X;Wang J;Lei X;Zhong J;Xian J;Quan Y;Lu Y;Huang Q;Chen J;Ge H;Feng H.
缺血性脑卒中是世界范围内导致死亡/长期残疾的主要疾病之一。激活内源性神经干/祖细胞（NSPCs），内衬在脑室下区（SVZ）和齿状回，促进损伤的脑组织恢复在短期和长期的实验设置。然而，只有少数增殖的NSPCs向损伤迁移以增强缺血后的内源性修复。结果表明，抗坏血酸（AA）在125 ~ 500 mg/Kg剂量范围内，能明显改善脑梗死大鼠的功能恢复，并能显著缩小梗死体积，且呈剂量依赖性，AA的适宜治疗浓度为250 mg/Kg。其机制可能与激活钠-维生素C协同转运体2（SVCT 2）有关，缺血后SVZ中SVCT 2表达下调。免疫组化结果显示，在生理和病理条件下，250 mg/Kg AA处理或SVCT 2过表达均可显著增加SVZ区的NSPCs迁移数量。此外，250 mg/Kg AA或SVCT 2过表达促进NSPCs迁移，其机制可能是通过在体外氧糖剥夺条件下上调CDC 42表达，促进F-actin组装。总之，本研究表明SVCT 2通过激活CDC 42促进F-actin组装促进NSPCs迁移，这扩大了AA的治疗范围以及SVCT 2在脑损伤后NSPCs迁移中的作用。
Ischemic stroke is one of the most leading diseases causing death/long-term disability worldwide. Activating endogenous neural stem/progenitors cells (NSPCs), lining in the subventricular zone (SVZ) and dentate gyrus, facilitates injured brain tissue recovery in both short and long-term experimental settings. While, only a few proliferated NSPCs migrate toward the lesions to enhance endogenous repair after ischemia. Here, the results indicated that the functional recovery was evidently improved and the infarct volume was significantly reduced with ascorbic acid (AA) treatment in a dose-dependent manner from 125 to 500 mg/Kg, and the suitable therapeutic concentration was 250 mg/Kg. The possible mechanism might be due to activating sodium-vitamin C cotransporter 2 (SVCT2), which was down-regulated in SVZ after ischemia. Furthermore, immunostaining images depicted the number of migrated NSPCs from SVZ were significantly increased with 250 mg/Kg AA treatment or SVCT2 overexpression under the physiological and pathological condition in vivo. Besides, the data also represented that 250 mg/Kg AA or SVCT2 overexpression facilitated NSPCs migration via promoting F-actin assembling in the manner of up-regulating CDC42 expression using oxygen-glucose deprivation in vitro. Collectively, the present study indicates that SVCT2 promotes NSPCs migration through CDC42 activation to facilitate F-actin assembling, which enlarges the therapeutic scope of AA and the role of SVCT2 in NSPCs migration after brain injury.
登录
查看更多内容
影响因子：
3
作者：
Wendl MC
通讯作者：
Wendl MC
人缪斯细胞在亚急性lacunar streos模型中重建神经元电路。
影响因子：
8.3
作者：
Uchida H;Niizuma K;Kushida Y;Wakao S;Tominaga T;Borlongan CV;Dezawa M
通讯作者：
Dezawa M
影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
聚 L-鸟氨酸通过促进 α-肌动蛋白 4 与肌动蛋白丝的结合来增强神经干/祖细胞的迁移。
影响因子：
4.6
作者：
Ge H;Yu A;Chen J;Yuan J;Yin Y;Duanmu W;Tan L;Yang Y;Lan C;Chen W;Feng H;Hu R
通讯作者：
Hu R
影响因子：
5.2
作者：
He, Xi-Biao;Kim, Mirang;Kim, Seon-Young;Yi, Sang-Hoon;Rhee, Yong-Hee;Kim, Taeho;Lee, Eun-Hye;Park, Chang-Hwan;Dixit, Shilpy;Harrison, Fiona E.;Lee, Sang-Hun
通讯作者：
Lee, Sang-Hun