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ENT1 Inhibition Attenuates Epileptic Seizure Severity Via Regulation of Glutamatergic Neurotransmission
Xu, Zucai1,2; Xu, Ping2; Chen, Yalan1; Liu, Jing1; Zhang, Yanke1; Lv, Yaodong1; Luo, Jing1; Fang, Min1; Zhang, Jun2; Wang, Jing2; Wang, Kewei3; Wang, Xuefeng1; Chen, Guojun1
关键词Epileptic seizure Type 1 equilibrative nucleoside transporter Nitrobenzylthioinosine Glutamatergic neurotransmitter
刊名NEUROMOLECULAR MEDICINE
2015-03-01
DOI10.1007/s12017-014-8338-2
17期:1页:1-11
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
资助者National Natural Science Foundation of China ; Guizhou Provincial Science and Technology Foundation ; National Natural Science Foundation of China ; Guizhou Provincial Science and Technology Foundation
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]EQUILIBRATIVE NUCLEOSIDE TRANSPORTER ; CENTRAL-NERVOUS-SYSTEM ; MICE LACKING ENT1 ; FUNCTIONAL-CHARACTERIZATION ; ADENOSINE LEVELS ; A(1) RECEPTORS ; MOUSE NEURONS ; EXPRESSION ; BRAIN ; FAMILY
英文摘要

Type 1 equilibrative nucleoside transporter (ENT1) promotes glutamate release by inhibition of adenosine signaling. However, whether ENT1 plays a role in epileptic seizure that involves elevated glutamatergic neurotransmission is unknown. Here, we report that both seizure rats and patients show increased expression of ENT1. Intrahippocampal injection of a specific inhibitor of ENT1, nitrobenzylthioinosine (NBTI), attenuates seizure severity and prolongs onset latency. In order to examine whether NBTI would be effective as antiepileptic after peripheral application, we injected NBTI intraperitoneally, and the results were similar to those obtained after intrahippocampal injection. NBTI administration leads to suppressed neuronal firing in seizure rats. In addition, increased mEPSC in seizure are inhibited by NBTI. Finally, NBTI results in deactivation of phosphorylated cAMP-response element-binding protein in the seizure rats. These results indicate that ENT1 plays an important role in the development of seizure. Inhibition of ENT1 might provide a novel therapeutic approach toward the control of epileptic seizure.

语种英语
所属项目编号81260201 ; 81271445 ; 81201003 ; [2013] 2327
资助者National Natural Science Foundation of China ; Guizhou Provincial Science and Technology Foundation ; National Natural Science Foundation of China ; Guizhou Provincial Science and Technology Foundation
WOS记录号WOS:000349910700001
Citation statistics
Cited Times:5[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67014
Collection北京大学药学院
作者单位1.Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China
2.Zunyi Med Coll, Affiliated Hosp, Dept Neurol, Zunyi 563003, Guizhou, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
Recommended Citation
GB/T 7714
Xu, Zucai,Xu, Ping,Chen, Yalan,et al. ENT1 Inhibition Attenuates Epileptic Seizure Severity Via Regulation of Glutamatergic Neurotransmission[J]. NEUROMOLECULAR MEDICINE,2015,17(1):1-11.
APA Xu, Zucai.,Xu, Ping.,Chen, Yalan.,Liu, Jing.,Zhang, Yanke.,...&Chen, Guojun.(2015).ENT1 Inhibition Attenuates Epileptic Seizure Severity Via Regulation of Glutamatergic Neurotransmission.NEUROMOLECULAR MEDICINE,17(1),1-11.
MLA Xu, Zucai,et al."ENT1 Inhibition Attenuates Epileptic Seizure Severity Via Regulation of Glutamatergic Neurotransmission".NEUROMOLECULAR MEDICINE 17.1(2015):1-11.
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