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The Role of Neural Stem Cell and Neural Plasticity in the Model of Epilepsy

神经干细胞和神经可塑性在癫痫模型中的作用

基本信息

批准号：
13670647
负责人：
SATO Keiko
金额：
$ 1.15万
依托单位：
Okayama University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670647/
关键词：
Epilepsy Neural Stem Cell Neural Plasticity Hippocampus Subventricular Zone キンドリング

项目摘要

To investigate the proliferation and migration of neural stem cells (NSC) as well as neural plastic changes in epileptic brain, spaciotemporal expressions of immunoreactive bromodeoxyuridine (BrdU) and highly polysialylated neural cell adhesion molecule (PSA-NCAM) were examined in amygdala kindling of rat.Amygdaloid kindling in partial seizure (PS) was effective in proliferation of NSC detected with BrdU-labeling in subventricular zone (SVZ), but not in dentate gyrus (DG). In SVZ, however, the BrdU-labeling cells decreased at 3 times generalized seizures (3 GS).The neural migration and synaptic remodeling detected with PSA-NCAM staining occurred in DG of hippocampus, subventricular zone and pyriform cortex with amygdaloid kindling in GS but not in PS. The number of PSA-NCAM positive cells in bilateral DG increased significantly at GS. Although total positive cell number was not significantly different between 3 GS and 30 times GS (30 GS) groups, a greater number of positive cells was located in the outer granule cell layer, and the immunopositive dendrite greatly extended to the molecular layer in 30 GS group. The number of PSA-NCAM positive cells increased 4 times in the bilateral SVZ at 3 GS, with a further increase at 30 GS.These facts indicate that proliferation of NSC increased with PS and decreased with severer seizures of GS in SVZ, and that such a proliferation did not occur in DG with PS or GS. Thus, the proliferation of NSC was spacially and temporally different between brain regions depending on different kindling stages. The increased migration of newly generated cells as well as plastic change of originally-existed neural cells may occur in response to the recurrent GS, which may contribute to abnormal reconstruction of synaptic network in hippocampus and epileptogenisity in kindling.

为探讨神经干细胞（NSC）在癫痫脑内的增殖、迁移和神经可塑性变化，本实验在大鼠杏仁核点燃中检测了免疫反应性溴脱氧尿苷（BrdU）和高度多唾液化神经细胞粘附分子（PSA-NCAM）的时空表达。部分癫痫发作（PS）时杏仁核体点燃对脑室下区（SVZ）的NSC增殖有效，但对齿状回（DG）的NSC增殖无效。然而，在SVZ中，brdu标记细胞在3次全面性癫痫发作（3gs）时减少。PSA-NCAM染色检测到海马、脑室下区和梨状皮质的神经迁移和突触重构发生在GS区，而PS区未见，双侧DG中PSA-NCAM阳性细胞数量显著增加。虽然3 GS组和30倍GS （30 GS）组的总阳性细胞数差异不显著，但30 GS组的阳性细胞较多位于外颗粒细胞层，免疫阳性树突向分子层延伸。3gs时双侧SVZ中PSA-NCAM阳性细胞数增加4倍，30gs时进一步增加。这些事实表明，SVZ中NSC的增殖随着PS的增加而增加，随着GS的严重发作而减少，而这种增殖在PS或GS的DG中没有发生。因此，根据不同的点燃阶段，脑区间NSC的增殖在空间和时间上存在差异。复发性GS可能导致新生细胞迁移增加，原有神经细胞可塑性改变，导致海马突触网络异常重建，点燃致痫。