海马苔藓纤维出芽及突触重组与颞叶癫痫的相关性研究

目的探讨颞叶癫痫（TLE）海马出芽苔藓纤维（MF）突触的超微结构特征在其发病机制中的作用以及神经轴突诱向因子netrin-1表达与MF突触重建的关系。方法锂-匹罗卡品诱导大鼠TLE,Timm组化染色标记出芽MF突触末端,在电镜下观察新生突触的超微结构特征。用原位杂交方法检测netrin-1在大鼠海马的表达。结果出芽MF突触主要是轴棘型非对称性突触,偶可看到出芽轴突和兴奋性颗粒细胞体形成突触联系。癫痫状态（SE）后7d,在海马齿状回颗粒细胞层可见netrin-1mRNA表达上调,并持续至SE后28d。其表达的时空顺序和海马MF出芽以及突触重组相一致。结论出芽MF突触的超微结构特性支持重组突触形成重复的兴奋性环路;神经轴突诱向因子netrin-1在出芽MF的靶向性生长和突触重组过程中可能起重要作用。

Correlation between hippocampal mossy fiber sprouting and synaptic reorganization and mechanisms of temporal lobe epilepsy

Objective To explore the effects of the ultrastructural features of sprouted mossy fiber synapses in the mechanism of temporal lobe epilepsy. To explore the correlation between axon guidance molecule-netrin-1 gene expression and mossy fiber synaptic reorganization Methods Sixty-one SD rats underwent intreperotoneal injection of lithium chloride and pilocarpin to establish models of status epilpticus characterized with temporal lobe epilepsy. Nineteen rats were used aa scontrols. One, 2, and 4 weeks after the injection, a certain numbers of rat were killed with their brains taken out. The sprouted mossy fiber synaptic terminals were labeled by Timm histochemistry and the ultrastructure of new synapses were observed by electron microscopy. By in situ hybridization, the mRNA expression of netrin-1 gene was observed Results The sprouted mossy fiber synapses in epileptic rats most commonly formed asymmetric synapses with dendritic spines and occasionally with granule cell somata. Seven days after the injection, up-regnlation of netrin-1 mRNA expression was seen in the dentate granule cell layers of hippocampus and continued to 4 weeks after the injection. The time course of the increase of netrin-1 mRNA in the dentate granule cell layers was correlated with the time course of mossy fiber sprouting and synaptic reorganization in hippocampus. Conclusion The ultrastructural features of sprouted mossy fiber synapses support the viewpoint that the reorganization of synapses prominently involves the formation of recurrent excitatory circuits. The axon guidance molecule- netrin-1 plays an important role in the process of mossy fiber axonal outgrowth and synaptogenesis in the hippocampal dentate gyms.