Chen Kevin, Henry Rebecca A, Hughes Stephanie M, Connor Bronwen
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Mol Cell Neurosci. 2007 Sep;36(1):108-20. doi: 10.1016/j.mcn.2007.06.004. Epub 2007 Jul 4.
Regional environmental cues present in the adult brain determine the fate of adult neural progenitor cells. To determine whether the growth factors BDNF or FGF2 can create a neurogenic environment outside the SVZ, we used AAV(1/2)-mediated gene transfer to produce ectopic BDNF or FGF2 expression in the normal adult rat striatum and transplanted SVZ-derived progenitor cells into this region. We observed that ectopic expression of BDNF in the striatum promoted neuronal differentiation of transplanted adult neural progenitor cells, while FGF2 expression supported the survival and proliferation of transplanted progenitor cells in the adult striatum. However, region-specific neuronal differentiation of transplanted progenitor cells was not observed in the adult striatum, suggesting ectopic BDNF or FGF2 expression was insufficient for the generation of mature neuronal phenotypes. This study provides direct in vivo evidence that ectopic striatal expression of either BDNF or FGF2 can induce neurogenesis in non-neurogenic regions of the adult brain.
成年大脑中存在的区域环境线索决定了成年神经祖细胞的命运。为了确定生长因子脑源性神经营养因子（BDNF）或成纤维细胞生长因子2（FGF2）是否能在侧脑室下区（SVZ）之外创造一个神经发生环境，我们使用腺相关病毒（AAV）（1/2）介导的基因转移，在正常成年大鼠纹状体中产生异位BDNF或FGF2表达，并将SVZ来源的祖细胞移植到该区域。我们观察到，纹状体中BDNF的异位表达促进了移植的成年神经祖细胞的神经元分化，而FGF2的表达则支持成年纹状体中移植的祖细胞的存活和增殖。然而，在成年纹状体中未观察到移植祖细胞的区域特异性神经元分化，这表明异位BDNF或FGF2表达不足以产生成熟的神经元表型。这项研究提供了直接的体内证据，即BDNF或FGF2在纹状体中的异位表达可诱导成年大脑非神经发生区域的神经发生。
