VEGF, a mediator of the effect of experience on hippocampal neurogenesis
VEGF, a mediator of the effect of experience on hippocampal neurogenesis
复制标题
DOI：
10.2174/156720506775697133
复制
发表时间：
2006-02-01
影响因子：
2.1
通讯作者：
Cao, Lei
中科院分区：
文献类型：
--
作者：
During, Matthew J.;Cao, Lei
啮齿动物生活在一个丰富的环境中，通过跑步锻炼或执行学习和记忆任务显示海马神经发生的增加。我们发现，无论是环境丰富，以及在瓷砖莫里斯水迷宫，一个依赖于学习任务，导致所有增加局部VEGF表达的大鼠。我们通过使用重组腺相关病毒（AAV）载体的体细胞基因转移在遗传上重现了这种情况。在成年大鼠中遗传性增加海马VEGF导致与认知改善相关的神经发生增加2倍。相比之下，胎盘生长因子（PGF）的基因转移，通过Flt1的信号，但不是KDR受体有负面影响的神经发生和抑制学习，虽然它同样增加了内皮细胞增殖。显性阴性mKDR的表达抑制基底神经发生和学习受损。共表达mKDR拮抗VEGF增强的神经发生和学习，而不抑制内皮细胞增殖。此外，通过RNA干扰抑制VEGF表达完全阻断了神经发生的环境诱导。这些数据支持一种模型，其中VEGF通过KDR起作用，是环境对神经发生和认知的影响的介导者[1]。
Rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show all increase in hippocampal neurogenesis. We show that both environmental enrichment, as well as performance in tile Morris water maze, a hippocampal-dependent learning task, leads to all increase in local VEGF expression in rats. We genetically recreated this situation by somatic cell gene transfer using recombinant adeno-associated virus (AAV) vectors. Genetically increasing hippocampal VEGF in adult rats resulted in a similar to 2 fold increase in neurogenesis associated with improved cognition. In contrast, gene transfer of placental growth factor (PGF) which signals through Flt1, but not KDR receptors had negative effects on neurogenesis and inhibited learning, although it similarly increased endothelial cell proliferation. Expression of a dominant negative, mKDR, inhibited basal neurogenesis and impaired learning. Co-expression of mKDR antagonized VEGF-enhanced neurogenesis and learning without inhibiting endothelial cell proliferation. Furthermore, inhibition of VEGF-expression by RNA interference completely blocked the environmental induction Of neurogenesis. These data support a model whereby VEGF acting via KDR is a mediator of the effect of the environment oil neurogenesis and cognition [1].