Increased glial glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus

Neurobiology of Disease

卷:47

Chien-Liang Glenn Lin¹  Kou Takahashi²  Yuchen Lin²  Qiongman Kong²  Delanie Schulte²  Nathan Stouffer² 

[1] Corresponding author at: Department of Neuroscience, The Ohio State University, 4198 Graves Hall, 333 W. 10th Avenue, Columbus, OH 43210, USA. Fax: [phone].;

[2] Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA;

关键词: Excitotoxicity;    Glutamate transporter;    EAAT2;    Temporal lobe epilepsy;    Pilocarpine;    Epileptogenesis;   

DOI  :  

来源: DOAJ

【 摘 要 】

Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased glial glutamate transporter EAAT2, the major glutamate transporter, could prevent seizure activity and reduce epileptogenic processes. EAAT2 transgenic mice, which have a 1.5–2 fold increase in EAAT2 protein levels as compared to their non-transgenic counterparts, were tested in a pilocarpine-induced status epilepticus (SE) model. Several striking phenomena were observed in EAAT2 transgenic mice compared with their non-transgenic littermates. First, the post-SE mortality rate and chronic seizure frequency were significantly decreased. Second, neuronal degeneration in hippocampal subfields after SE were significantly reduced. Third, the SE-induced neurogenesis and mossy fiber sprouting were significantly decreased. The severity of cell loss in epileptic mice was positively correlated with that of mossy fiber sprouting and chronic seizure frequency. Our results suggest that increased EAAT2 expression can protect mice against SE-induced death, neuropathological changes, and chronic seizure development. This study suggests that enhancing EAAT2 protein expression is a potential therapeutic approach.

【 授权许可】

Unknown