The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain
The FGF-2/FGFRs neurotrophic system promotes neurogenesis in the adult brain
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DOI：
10.1007/s00702-009-0207-z
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发表时间：
2009-08-01
影响因子：
3.3
通讯作者：
Belluardo, Natale
中科院分区：
文献类型：
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作者：
Mudo, G.;Bonomo, A.;Belluardo, Natale
神经发生发生在成人大脑的两个区域，即侧脑室壁的脑室下区（SVZ）和海马结构齿状回（DG）的颗粒下区（SGZ）。成体神经发生需要几种神经营养因子来维持和调节成体干细胞群的增殖和分化。在本综述中，我们研究成纤维细胞生长因子-2（FGF-2）及其受体（FGFRs）介导的营养系统的细胞和功能方面的神经发生在SVZ和SGZ的成年大鼠大脑。在SVZ中，FGF-2在SVZ的GFAP阳性细胞中表达，但不存在于增殖前体细胞中，增殖前体细胞反而表达FGFR-1和FGFR-2，但不表达FGFR-3 mRNA（尽管在SVZ中表达）和FGFR-4。因此，似乎在SVZ中，FGF-2可以由不同于前体细胞谱系的GFAP阳性细胞释放，并且通过体积传递到达增殖的前体细胞。FGFR-1 mRNA也在SGZ中表达，并位于BrdU标记的前体细胞中，而FGFR-2和FGFR-3 mRNA虽然在SGZ中表达，但不位于增殖的前体细胞中。在老年大鼠SVZ和DG中增殖前体细胞的年龄相关性下降已被充分记录，并且有一种建议，即部分可能是生长因子表达水平改变的结果。因此，旧的前体细胞可能会对生长因子产生反应，这表明在衰老过程中，神经元前体细胞增殖的基本成分被保留，并且在适当的刺激后增加神经发生的能力仍然保留。总之，FGF-2及其受体介导的营养系统有助于创造一个重要的微环境生态位，促进成人和老年人大脑中的神经发生。
Neurogenesis occurs in two regions of the adult brain, namely, the subventricular zone (SVZ) throughout the wall of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG) in hippocampal formation. Adult neurogenesis requires several neurotrophic factors to sustain and regulate the proliferation and differentiation of the adult stem cell population. In the present review, we examine the cellular and functional aspects of a trophic system mediated by fibroblast growth factor-2 (FGF-2) and its receptors (FGFRs) related to neurogenesis in the SVZ and SGZ of the adult rat brain. In the SVZ, FGF-2 is expressed in GFAP-positive cells of SVZ but is not present in proliferating precursor cells, which instead express FGFR-1 and FGFR-2, but not FGFR-3 mRNA, although expressed in the SVZ, and FGFR-4. Therefore, it seems that in the SVZ FGF-2 may be released by GFAP-positive cells, different from the precursor cell lineage, and via volume transmission it reaches the proliferating precursor cells. FGFR-1 mRNA is also expressed in the SGZ and is localized in BrdU-labeled precursor cells, whereas FGFR-2 and FGFR-3 mRNA, although expressed in the SGZ, are not located within proliferating precursor cells. An aged-related decline of proliferating precursor cells in the SVZ and DG of old rats has been well documented, and there is the suggestion that in part it could be the consequence of alterations in growth factor expression levels. Thus, the old precursors may respond to growth factors, suggesting that during aging the basic components for neuronal precursor cell proliferation are retained and the capacity to increase neurogenesis after appropriate stimulation is still preserved. In conclusion, the trophic system mediated by FGF-2 and its receptors contributes to create an important micro-environmental niche that promotes neurogenesis in the adult and aged brain.