Studies on signal transduction system in absence seizures

在这项研究中，我研究了与环AMP反应元件结合蛋白（CREB）激活相关的信号转导途径，CREB是一种转录因子，在全局性失神发作中。γ-羟基丁酸（GHB）模型小鼠（药物诱导模型）和嗜睡（lh/lh）模型小鼠（遗传模型）大脑皮层和丘脑中cre结合活性均显著高于各对照组小鼠。在两种模型小鼠的海马和小脑中均未观察到这些增加。Western blot分析显示，两种模型小鼠的大脑皮层和丘脑的磷酸CREB （pCREB）免疫反应活性均高于对照小鼠，而海马和小脑的磷酸CREB免疫反应活性与对照小鼠无显著差异。嗜睡小鼠（lh/lh）大脑皮层和丘脑的CREB结合蛋白（CBP）免疫反应活性高于对照组。激活转录因子（ATF6）是CREB/ATF家族的成员，也是内质网（ER）应激诱导的转录因子，嗜睡（lh/lh）小鼠丘脑的免疫反应性低于对照组。此外，嗜睡小鼠（lh/lh）丘脑葡萄糖调节蛋白78 （GRP78）免疫反应性显著低于对照组。这些数据表明，cre结合活性的增加是由于pCREB结合活性的激活，嗜睡（lh/lh）小鼠而非GHB模型小鼠出现ER应激伴失神发作。

In this study, I examined the signal transduction pathway associated with activation of cyclic AMP responsive element binding protein (CREB), a transcription factor, in generalized absence seizures. In γ-hydroxybutylic acid (GHB) model mice, a drug-induced model, and lethargic (lh/lh) mice, a genetic model, CRE-binding activities in the cerebral cortex and thalamus were significantly higher than those in each control mice. These increases were not observed in the hippocampus or cerebellum in both model mice. Western blot analysis revealed that phosphoCREB (pCREB) but not CREB immunoreactivities in the cerebral cortex and thalamus in both model mice were higher than in each control mice, whereas there were no difference between the two in the hippocampus and cerebellum. CREB binding protein (CBP) immunoreactivities in the cerebral cortex and thalamus in the lethargic (lh/lh) mice were higher than those in control mice. The activating transcription factor (ATF6), a member of CREB/ATF family and an endoplasmic reticulum (ER) stress-induced transcription factor, immunoreactivity in the thalamus in lethargic (lh/lh) mice was lower than that in control mice. In addition, thalamic glucose-regulated protein 78 (GRP78) immunoreactivity in lethargic (lh/lh) mice was significantly lower than that in control mice. These data revealed that the increased CRE-binding activity was attributable to activation of the binding activity of pCREB and that lethargic (lh/lh) mice but not GHB model received ER stress accompanied with absence seizures.