Morris Daniel C, Zhang Zheng Geng, Wang Ying, Zhang Rui Lan, Gregg Sara, Liu Xian Shuang, Chopp Michael
Henry Ford Health Systems, Department of Emergency Medicine, CFP-2, 2799 West Grand Blvd, Detroit, MI 48202, USA.
Neurosci Lett. 2007 May 17;418(2):170-4. doi: 10.1016/j.neulet.2007.03.039. Epub 2007 Mar 23.
Neurogenesis occurs in adult brain neural progenitor cells (NPCs) located in the subventricular zone (SVZ) of the lateral ventricle and the subgrandular zone of the hippocampal dentate gyrus. After ischemic stroke, NPCs in the SVZ proliferate and migrate towards the ischemic boundary region to replenish damaged neurons. During development, the Wnt pathways contribute to stem cell maintenance and promote neurogenesis. We hypothesized that stroke up regulates Wnt family genes in SVZ cells. Non-ischemic and ischemic cultured SVZ cells and a single population of non-ischemic and ischemic SVZ cells isolated by laser capture microdissection (LCM) were analyzed for Wnt pathway expression using real-time RT-PCR and immunostaining. The number of neurospheres increased significantly (p<0.05) in SVZ cells derived from ischemic (32+/-4.7/rat) compared with the number in non-ischemic SVZ cells (18+/-3/rat). Wnt family gene mRNA levels were detected in SVZ cells isolated from both cultured and LCM SVZ cells, however there was no up regulation between non-ischemic and ischemic SVZ cells. Immunostaining on brain sections also demonstrated no up regulation of Wnt pathway protein between ischemic and non-ischemic SVZ cells. Expression of the Wnt family genes in SVZ cells support the hypothesis that the Wnt pathway may be involved in neurogenesis in the adult brain. However, ischemia does not up regulate Wnt family gene expression.
神经发生在位于侧脑室室下区(SVZ)和海马齿状回颗粒下区的成体脑神经祖细胞(NPC)中。缺血性中风后,SVZ中的NPC增殖并向缺血边界区域迁移以补充受损神经元。在发育过程中,Wnt信号通路有助于干细胞维持并促进神经发生。我们假设中风会上调SVZ细胞中Wnt家族基因的表达。使用实时RT-PCR和免疫染色分析了非缺血和缺血培养的SVZ细胞以及通过激光捕获显微切割(LCM)分离的单一非缺血和缺血SVZ细胞群体的Wnt信号通路表达。与非缺血SVZ细胞(18±3/只大鼠)相比,缺血来源的SVZ细胞(32±4.7/只大鼠)中神经球数量显著增加(p<0.05)。在从培养的和LCM分离的SVZ细胞中均检测到Wnt家族基因的mRNA水平,然而非缺血和缺血SVZ细胞之间没有上调。脑切片的免疫染色也表明缺血和非缺血SVZ细胞之间Wnt信号通路蛋白没有上调。SVZ细胞中Wnt家族基因的表达支持Wnt信号通路可能参与成体脑神经发生的假设。然而,缺血并不会上调Wnt家族基因的表达。