糖皮质激素与癫痫脑内突触肌动蛋白骨架稳定性的研究

The rearrangement of F-actin in the epileptic brain has been proved in our previous study and is probable relation to epileptogenesis. In addition, there is growing concern on the role of glucocorticoids in treatment of the refractory epilepsy clinically. Studies have shown that glucocorticoids can regulate the morphology of dentritic spines through activating the glucocorticoid receptors (GRs) in the dentritic membrane. Thus we deduce that the glucocorticoids can stabilize the F-actin cytoskeleton, reduce the synaptic remodeling through GRs, which localized in the dendritic spines, and then block the excitatory network in epileptic brain. In the current study, we will examin the change of F-actin dynamics in the epileptic model induced by pilocarpine together with the agonist (Dex) and antagonist (RU486) of GRs respectively. Using immune fluorescent staining, pre-/postsynaptic labeling and protein techniques, we try to detect the influence of glucocorticoids on the F-actin remodeling in epileptic brain from synaptic level and expore the possibilities of blocking the epileptogenesis through stablizing F-actin cytoskeleton, which will be a novel approach for epilepsy treatment.

我们在前期研究发现，癫痫脑内突触肌动蛋白骨架（F-actin）表达显著减少并伴有分布和形态学改变，这一发现表明F-actin重构与癫痫灶的形成密切相关。另外，近年来临床上开始用糖皮质激素治疗一些难治性癫痫。已有研究显示糖皮质激素能够通过激活树突棘膜上的糖皮质激素受体影响树突棘的形态。因此我们推测糖皮质激素很可能是通过作用于树突棘上的糖皮质激素受体来稳定F-actin细胞骨架，进而减少突触异常重塑，从而有效地阻断癫痫脑内兴奋性网络的构建。本研究通过匹鲁卡品慢性癫痫模型，在激活和抑制糖皮质激素受体两种不同情况下分析F-actin动力学变化，通过免疫荧光检测，结合突触前后成分标记以及突触神经体蛋白分析等技术，从突触水平探讨慢性癫痫中糖皮质激素在F-actin重构中的作用，探讨稳定F-actin骨架阻断癫痫灶形成的可能性，为治疗癫痫开辟崭新的途径。

我们在前期研究发现，癫痫脑内突触肌动蛋白骨架（F-actin）表达显著减少并伴有分布和形态学改变，这一发现表明F-actin重构与癫痫灶的形成密切相关。另外，近年来临床上开始用糖皮质激素治疗一些难治性癫痫。已有研究显示糖皮质激素能够通过激活树突棘膜上的糖皮质激素受体影响树突棘的形态。因此我们推测糖皮质激素很可能是通过作用于树突棘上的糖皮质激素受体来稳定F-actin细胞骨架，进而减少突触异常重塑，从而有效地阻断癫痫脑内兴奋性网络的构建。本研究通过匹鲁卡品癫痫模型，在干预糖皮质激素受体情况下分析F-actin动力学变化，通过免疫荧光检测，结合突触前后成分标记以及蛋白分析等技术，从突触水平探讨癫痫中糖皮质激素在Factin重构中的作用，探讨稳定F-actin骨架阻断癫痫灶形成的可能性，为治疗癫痫开辟崭新的途径