Protective effects of EAAT2 over-expression on a mouse model of pilocarpine-induced status epileptics

CAO Ruifeng; ZHANG Xiang; ZHANG Wei; LIN Yuan; WANG Lina

doi:10.3969/j.issn.1671-2897.2007.06.002

Abstract：Objective The purpose of this experiment is to study the effect of excitatory amino acid transporter 2(EAAT2) over expression on status epileptics (SE) and SE-induced neuronal death. Methods The mouse SE models were established by intraperitoneal injection of pilocarpine on EAAT2 transgenic mice and wildtype mice. Three days after SE, brains were harvested and cut into 40 m sections. EAAT2 level was determined by immunostaining. Survived neurons were detected by cresyl violet staining. Somatostatin-positive neurons were also detected by immunostaining. Cell numbers in hippocampal CA1 and hilus of dentate gyrus were counted and compared between the transgenic and wild-type animals. Results Compared with the wild-type animals, EAAT2was over-expressed in the transgenic mice. A significant larger dose of pilocarpine was needed to induce SE in EAAT2 transgenic mice, compared with the dose for the wild-type animals (657 ± 119.9 mg/kg, n =4 vs 344 ±40.3 mg/kg, n =4; P＜0.05). Three days after SE, the relative pyramidal cell number in CA1 was 0.56 in the wild-type mice, while the relative cell number was 0. 9 in the EAAT2 transgenic animals. The post-SE cell number in the hippocampus CA1 pyramidal layer was higher in the EAAT2 transgenic mice than that in the wildtype animals. In the DG hilus, the relative post-SE cell numbers were 0. 11 and 0.67 in the wild-type animals and EAAT2 transgenic mice, respectively. In the wild-type animals, the relative number of somatostain-positive cells was 0 in the DG hilus after SE. However, the number was 0. 4 in the EAAT2 transgenic mice. Conclusion Our results indicate that over-expressed EAAT2 has significant protective effect on SE and SE-induced neuronal death.Over-expressed EAAT2 may modulate the excitotoxity during seizure by enhancing extracellular glutamate uptake.