Asanuma M, Nishibayashi S, Kondo Y, Iwata E, Tsuda M, Ogawa N
Department of Neuroscience, Okayama University Medical School, Japan.
Brain Res Mol Brain Res. 1995 Oct;33(1):29-36. doi: 10.1016/0169-328x(95)00102-x.
Using electrophoretic mobility-shift assay (EMSA), we examined changes in DNA-binding activities of transcriptional factor-activated protein-1 (AP-1), which is a Fos-Jun protein complex, onto its responsive element TRE in the hippocampus and amygdaloid nucleus of rats stimulated with pentylenetetrazol (PTZ) injection, and also investigated the effects of a single administration of the immunosuppressant cyclosporin A (CsA). In EMSA with nuclear extracts from the rat brain, the TRE-binding activity of AP-1 in the hippocampus and amygdaloid nucleus markedly increased 2 h after the PTZ injection (75 mg/kg, i.p.). These PTZ-induced increases of the TRE-binding protein in these regions were completely suppressed, by pretreatment with CsA (5 mg/kg, s.c.) 1 h before the PTZ injection. In addition, the administration of CsA significantly ameliorated PTZ-induced convulsion. This therapeutic effect of single CsA pretreatment may be based, in part, on the effects on the TRE-binding activity of AP-1 in the brain. Since single pretreatment of CsA in the present study had no effect on the PTZ-induced induction of c-fos mRNA, c-jun mRNA, Fos protein nor Jun protein, the inhibitory effects of single CsA administration on PTZ-induced TRE-binding activity in the brain may be related to the effects of CsA on AP-1 itself. These results suggest that an immune response via activation of transcriptional factor in the brain tissue is involved in the convulsion.
利用电泳迁移率变动分析（EMSA），我们检测了转录因子激活蛋白-1（AP-1，一种Fos-Jun蛋白复合物）在经戊四氮（PTZ）注射刺激的大鼠海马体和杏仁核中，与其反应元件TRE的DNA结合活性的变化，并且还研究了单次给予免疫抑制剂环孢素A（CsA）的作用。在对大鼠脑组织核提取物进行的EMSA实验中，PTZ注射（75mg/kg，腹腔注射）2小时后，海马体和杏仁核中AP-1的TRE结合活性显著增加。在PTZ注射前1小时用CsA（5mg/kg，皮下注射）预处理，可完全抑制PTZ诱导的这些区域中TRE结合蛋白的增加。此外，给予CsA可显著改善PTZ诱导的惊厥。单次CsA预处理的这种治疗效果可能部分基于其对脑中AP-1的TRE结合活性的影响。由于本研究中单次CsA预处理对PTZ诱导的c-fos mRNA、c-jun mRNA、Fos蛋白和Jun蛋白的诱导没有影响，单次给予CsA对PTZ诱导的脑中TRE结合活性的抑制作用可能与CsA对AP-1本身的作用有关。这些结果表明，脑组织中转录因子激活介导的免疫反应与惊厥有关。
