脑源性神经营养因子与海马苔藓状纤维突触重组的关系  

Relation between BDNF and synaptic reorganization of hippocampal mossy fibers

作　　者：赵世刚[1] 姜玉武[2] 罗强[2] 吴希如[2] 

机构地区：[1]内蒙古医学院第一附属医院神经内科,010050 [2]北京大学第一医院儿科神经组,100034

出　　处：《中华医学杂志》2001年第5期283-287,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目! (3 9670 2 65 )

摘　　要：目的　探讨海马苔藓状纤维 (mossyfiber,MF)突触重组过程与脑源性神经营养因子(brain derivedneurotrophicfactor,BDNF)的关系。方法　大鼠脑室内分别注射BDNF反义寡核苷酸、正义寡核苷酸和磷酸盐缓冲液 ,采用Timm′s染色法观察BDNF反义寡核苷酸对于红藻氨酸 (kainicacid ,KA)癫痫模型以及非KA模型海马MF发芽过程的影响。结果　采用计算机显微图像分析系统对Timm′s染色脑片海马齿状回内分子层 (innermolecularlayer,IML)异常Timm染色颗粒定量测定发现 ,KA能导致大鼠海马MF出现明显的发芽现象 ,KA模型组IML异常Timm颗粒吸光度 (6 8.0 )显著高于非KA模型组 (2 5 .5 ) (P <0 .0 0 1) ;而脑室内注射BDNF反义寡核苷酸能够抑制大鼠KA模型海马MF发芽过程 ,注射BDNF反义寡核苷酸的KA模型组IML异常Timm颗粒吸光度 (4 2 .0 )显著低于注射正义寡核苷酸的KA模型组 (6 8.0 ;P <0 .0 0 1) ;KA能导致大鼠海马各区BDNF蛋白表达显著增高 ,脑室内注射BDNF反义寡核苷酸能够抑制大鼠KA模型惊厥所引起的海马BDNF表达上调。结论　在MF突触重组过程中 ,BDNF的作用很可能是促进了癫痫时反复惊厥所导致的MF发芽过程。脑室内注射BDNF反义寡核苷酸对海马MF突触重组的影响作用很可能是通过抑制BDNF蛋白合成而产生的。Objective To investigate the relation between brain-derived neurotrophic factor (BDNF) and synaptic reorganization of hippocampal fibers (MF). Methods Antisense or sense oligomucleotides to BDNF and/or PBS buffer were injected into the cerebal ventricles of rats of epileptic model induced by kainic acid (KA) and control rats respectively. Immunohistochemical staining and Timm's silver sulfide staining were used to examine the effect of antisense oligonucleotides to BDNF upon the MF sprouting in the KA model and control rats. Results Timm's staining showed that multiple aberrant Timm's granules were found in the inner molecular layer (IML) of the dentate gyrus of hippocampus of the KA model rats intracerebroventricularly injected with sense oligonucleotides to BDNF or PBS, less aberrant Timm's granules were found in the hippocampal IML of KA model rats intracerebroventricularly injected with antisense oligonucleotides to BDNF, and no aberrant Timm's granule was found in the hippocampal IML of non-KA model rats intracerebroventricular injected with antisense oligonucleotides to BDNF. Immunohistochemical staining showed multiple BDNF immunologically labeled neurons in the hilus and CA3 region of hippocampus of KA model rats intracerebroventricularly injected with sense oligonucleotides to BDNF and PBS, less in the KA model rats intracerebroventricularly injected with antisense oligonucleotides to BDNF, and only a few in the non-KA model rats. The A value in both Timm's and immunohistochemical sections of KA model rats was higher than that of non-KA model rats. The A value in both Timm's and immunohistochemical sections of KA model rats was significantly lower in the groups injected with antisense oligonucleotides to BDNF than in the group injected with sense oligonucleotides. Conclusion BDNF may play an important role in promoting the MF sprouting caused by repeated epileptic convulsion in the course of MF synaptic reorganization. The expression of BDNF protein can be upregulated by subcutaneous injection of KA

关 键 词：癫痫 脑源性神经营养因子 苔藓纤维 海马 突触重组 

分 类 号：R742.1[医药卫生—神经病学与精神病学]