ENT1 Inhibition Attenuates Epileptic Seizure Severity Via Regulation of Glutamatergic Neurotransmission

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• 作者：Zucai Xu (1) (2)
  Ping Xu (2)
  Yalan Chen (1)
  Jing Liu (1)
  Yanke Zhang (1)
  Yaodong Lv (1)
  Jing Luo (1)
  Min Fang (1)
  Jun Zhang (2)
  Jing Wang (2)
  Kewei Wang (3)
  Xuefeng Wang (1)
  Guojun Chen (1)
  
  1. Department of Neurology ; The First Affiliated Hospital ; Chongqing Medical University ; 1 Youyi Road ; Chongqing ; 400016 ; China
  2. Department of Neurology ; Affiliated Hospital of Zunyi Medical College ; 149 Dalian Road ; Zunyi ; 563003 ; Guizhou ; China
  3. Pharmaceutical Sciences School of Peking University ; Beijing ; 100083 ; China
  
• 关键词：Epileptic seizure ; Type 1 equilibrative nucleoside transporter ; Nitrobenzylthioinosine ; Glutamatergic neurotransmitter
• 刊名：NeuroMolecular Medicine
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：17
• 期：1
• 页码：1-11
• 全文大小：7,816 KB
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• 刊物主题：Neurosciences; Neurology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-1174

文摘

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.