Hyper Sensitivity of the Brain of Epileptogenic E1 Mice to Vestibular Neuronal Stimulation

EL小鼠是人类癫痫的既定动物模型。这些小鼠对一些重复的感官刺激表现为癫痫发作，并迅速加速运动，如被抛起或海浪运动。虽然这种技术传统上被用来在这些小鼠身上诱发癫痫发作，但刺激的含义仍然不清楚。此前，我们已经证明，与ddy鼠(“母系”)相比，El鼠脑内3-羟基邻氨基苯甲酸双加氧酶(3-HAO)的表达增加，qumolinic酸(一种兴奋性毒素)的合成增加。本研究的目的是研究抛起刺激对这些小鼠脑内3-HAO和c-fos表达的影响。结果表明，周期性重复抛起刺激可引起EL小鼠脑内3-HAO和c-fos的表达增加。相比之下，刺激对ddy小鼠大脑中这些基因的表达没有影响。这些现象不是癫痫引起的神经元激活的结果，因为c-fos的诱导只发生在单一的翻腾刺激之后，远远早于癫痫发作的出现时间。这些结果表明，EL小鼠对前庭刺激具有遗传上的高敏感性，导致3-HAO的表达增强，这可能是小鼠癫痫发生的遗传基础。

The El mice are an established animal model for human epilepsy. These mice manifest seizures in response to some repeated sensory stimuli with rapidly accelerated movements such as being tossed-up or seasaw movements. Although this technique has been traditionally employed to induce seizures in these mice, the meaning of the stimuli remained obscure. Previously we have shown increased synthesis of qumolinic acid, an excitotoxin, with enhanced expression of 3-hydroxyanthranilate 3,4-dioxygenase (3-HAO) in the brain of El mice as compared with that of ddY mice (the "mother strain"). The aim of this study was to examine the effects of tossing-up stimuli on expression of 3-HAO and c-fos, a well known marker of neuronal activation, in the brain of these mice. The results obtained demonstrate that periodically repeated tossing-up stimuli caused increased expression of 3-HAO and c-fos in the brain of El mice. In contrast, the stimuli had no effect on the expressison of these genes in the brain of ddY mice. These phenomena were not consequences of neuronal activation caused by seizures, since c-fos induction occurred only after single tossing-up stimuli, far earlier than the time manifesting seizures. These results suggest that El mice are genetically hyper-sensitive to vestibular stimuli, resulting in enhanced expression of 3-HAO.This may be a genetic basis for the epileptogenesis of the mice.