신생 흰쥐의 해마에서 에스트로젠 투여가 N-methyl-D-aspartate 에 의한 신경독성에 미치는 영향

Abstract

Objective: To examine the in vivo effect of estradiol on neuronal death in the hippocampus of Sprague-Dawley rats which is most vulnerable to neurodegenerative changes. Material & Method : The three 3-weeks old neonatal rats were administered subcutaneously by β-estradiol 17-propionate 50nM 100㎕, and other three rats were administered subcutaneously by β-estradiol 17-propionate 100nM 100㎕. There six rats were administered intraperitoneally by NMDA(100μM)100㎕, 24hrs after estrogen administration. The other three rats were administered subcutaneouly by vehicle and intraperitoneally NMDA 24 hrs later. We used three rats administered only by vehicle as control group. We extracted and homogenate the hippocampus 6 hrs after the last administration. The samples were analyzed for LDH activities using non-denaturing polyacrylamide gel electrophoresis, isoenzyme activity staining and densitometer. All analysis were performed in triplicate. Results : If the enzyme activity of control group is 1, the relative activity of group administered by β-estradiol 17-propionate 50nM 100㎕ and NMDA was 0.9725±0.0014(mean±SD)which was not statistically different to control group . But that of group administered by β-estradiol 17-propionate 100nM 100㎕ and NMDA was 1.1359±0.0120which was significantly higher than other three groups (P<0.05). That of group administered only by NMDA was 0.9037±0.0136 which was significantly lower than other three groups (P<0.05). Conclusion : The released LDH (a typical sign of necrotic cell death) from cells into the surrounding tissue is destroyed readily by the existing enzymes. So the activities of LDH in hippocampus after NMDA exposure in vivo experiments reflected the number of alive neurons, which is in contrast to in vitro study. These data indicates that intraperitoneally administered NMDA induces the neurotoxicity in the hippocampus and the estrogen decrease the NMDA neurotoxicity, which may be dose-dependent.