التفاصيل البيبلوغرافية
| العنوان: |
Endothelial Cdk5 deficit leads to the development of spontaneous epilepsy through CXCL1/CXCR2-mediated reactive astrogliosis |
| المؤلفون: |
Liu, Xiu-xiu, Yang, Lin, Shao, Ling-xiao, He, Yang, Wu, Gang, Bao, Yu-huan, Lu, Nan-nan, Gong, Dong-mei, Lu, Ya-ping, Cui, Tian-tian, Sun, Ning-he, Chen, Dan-yang, Shi, Wei-xing, Fukunaga, Kohji, Chen, Hong-shan, Chen, Zhong, Han, Feng, Lu, Ying-mei |
| المساهمون: |
National Key Research and Development Program of China, National Natural Science Foundation of China, Nanjing Medical University |
| المصدر: |
Journal of Experimental Medicine ; volume 217, issue 1 ; ISSN 0022-1007 1540-9538 |
| بيانات النشر: |
Rockefeller University Press |
| سنة النشر: |
2019 |
| الوصف: |
Blood–brain barrier (BBB) dysfunction has been suggested to play an important role in epilepsy. However, the mechanism mediating the transition from cerebrovascular damage to epilepsy remains unknown. Here, we report that endothelial cyclin-dependent kinase 5 (CDK5) is a central regulator of neuronal excitability. Endothelial-specific Cdk5 knockout led to spontaneous seizures in mice. Knockout mice showed increased endothelial chemokine (C-X-C motif) ligand 1 (Cxcl1) expression, decreased astrocytic glutamate reuptake through the glutamate transporter 1 (GLT1), and increased glutamate synaptic function. Ceftriaxone restored astrocytic GLT1 function and inhibited seizures in endothelial Cdk5-deficient mice, and these effects were also reversed after silencing Cxcl1 in endothelial cells and its receptor chemokine (C-X-C motif) receptor 2 (Cxcr2) in astrocytes, respectively, in the CA1 by AAV transfection. These results reveal a previously unknown link between cerebrovascular factors and epileptogenesis and provide a rationale for targeting endothelial signaling as a potential treatment for epilepsy. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1084/jem.20180992 |
| DOI: |
10.1084/jem.20180992/1762510/jem_20180992.pdf |
| الإتاحة: |
https://doi.org/10.1084/jem.20180992Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.F90CDF04 |
| قاعدة البيانات: |
BASE |
