神经营养因子-3在颞叶癫癎后的表达与海马苔藓纤维发芽的关系

Correlation between neurotrophin-3 and mossy fibers sprouting in hippocampus after temporal epilepsy

目的探讨神经营养因子-3(NT-3)在颞叶癫癎大鼠海马内表达与苔藓纤维发芽(MFS)的可能关系。方法大鼠侧脑室注射红藻氨酸(KA)建立颞叶癫癎模型后,侧脑室注射NT-3反义寡核苷酸(ASODN)及正义寡核苷酸(SODN);应用免疫组化法观察海马NT-3表达;应用Timm银染方法,光镜和电镜观察海马MFS,并与空白对照组及脂质体对照组进行比较。结果致癎后大鼠海马齿状回NT-3表达下降;海马苔藓纤维明显粗乱,侧支发芽;齿状回内分子层可见银标记突触末端,主要为轴-树型非对称突触,其中ASODN组海马NT-3蛋白水平降低及MFS程度更明显。结论 KA致癎和NT-3 ASODN均能降低大鼠海马齿状回NT-3表达,增加MFS程度。提示NT-3可能通过对MFS及突触重组作用来影响颞叶癫癎的发生和发展。

Objective To investigate the potential relation of abnormal neural circuits and express changes of neurotrophin-3（NT-3） in hippocampus of experimental temporal epilepsy rats.Methods Built experimental temporal epilepsy models of rats by injecting kainic acid（KA） in lateral ventricle of adult rats,injected NT-3 antisense oligonucleotide（ASODN） and sense oligonucleotide（SODN）,then measure the expression of NT-3 in hippocampus of rats by immunohistochemistry.Mossy fiber sprouting（MSF） and synapse restitution in hippocampus were Neo-Timm silver stained and examined by light microscope and electron microscope.The result were be compared with blank group and lipid control group.Results Expression level of NT-3 in hippocampus dentate gyrus of temporal epilepsy rats decreased while MSF was obvious in hippocampus,and collateral sprouting.Silver stained synapses were found in dentate gyrus stratum moleculare,and the majority of these synapses were axo-spinous synapses.In ASODN group,the expression level of NT-3 was effectively down and MSF was to a higher extent in hippocampus.Conclusions Expression level of NT-3 in hippocampus dentate gyrus of rats can be decreased by KA and NT-3 ASODN injection,and MSF obviously increased in hippocampus,that NT-3 can inhibit the MFS.The inhibitory action of NT-3 on MFS and synaptic reorganization possibly may effected occurrence and development of temporal epilepsy.