Dynamic changes of the gene, protein and neural progenitors in the monkey hippocampus after ischemia

缺血后猴海马基因、蛋白及神经祖细胞的动态变化

基本信息

批准号：
15390432
负责人：
YAMASHIMA Tetsumori
金额：
$ 7.23万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The followings are main findings of the past three years, using a model of cerebral injury-global ischemia.1)We found that ischemia can increase the number of NPC in adult monkey hippocampus similarly to the rodent brain, but the monkey response was much lower than the rodent response-10 times in quantity, and more importantly-15 times in ability to produce neurons (neuronal differentiation) (Mol Cell Neurosci 23:292-301,2003).2)Further, monkey NPC were unable to replace any neurons in the ischemia-vulnerable CA1 sector (Glia 42;209-224,2003), which suggests that they cannot mediate a clinically-significant effect without an external influence.3)Recently, we have identified potential molecular explanation for this discrepancy between rodent and monkey NPC-while rodent NPC in CA1 sector express the developmental transcription factors Pax6,Emx2 and Ngn2 that can promote neurogenesis, monkey NPC in CA1 did not express these proteins.4)Importantly, we have identified a vascular niche around the adventitia of blood vessels that can promote neurogenesis in monkey dentate gyrus but not in CA1 sector (Hippocampus 14:861-875,2004).5)Lastly, we were the first to describe postischemic NPC upregulation in SVZ of the lateral ventricle, also in the olfactory bulb, and a limited neuronal production in the postischemic monkey neocortex and striatum (J Neurosci Res 81:776-788,2005).6)Thus, the applicant's group has investigated all major regions in the primate telencephalon with respect to postischemic neurogenesis.

The followings are main findings of the past three years, using a model of cerebral injury-global ischemia.1)We found that ischemia can increase the number of NPC in adult monkey hippocampus similarly to the rodent brain, but the monkey response was much lower than the rodent response-10 times in quantity, and more importantly-15 times in ability to produce neurons (neuronal differentiation) (Mol Cell Neurosci 23：292-301,2003）.2）此外，猴子NPC无法替代可缺血的CA1部门中的任何神经元（GLIA 42; 209-224,2003），这表明它们无法介导临床上有意义的效应而没有外部影响。 rodent NPC in CA1 sector express the developmental transcription factors Pax6,Emx2 and Ngn2 that can promote neurogenesis, monkey NPC in CA1 did not express these proteins.4)Importantly, we have identified a vascular niche around the adventitia of blood vessels that can promote neurogenesis in monkey dentate gyrus but not in CA1 sector (Hippocampus 14：861-875,2004）.5）最后，我们是第一个描述外侧心室中缺血后NPC上调的人，在嗅球中也是在嗅球中，以及在后卫星后的神经元中的神经元产生有限的神经元产生（J Neurospi res 81：776-776-78，200555555）灵长类动物尾脑中的主要区域相对于缺血后神经发生。