Mudò G, Bonomo A, Di Liberto V, Frinchi M, Fuxe K, Belluardo Natale
Department of Experimental Medicine, Division of Human Physiology, University of Palermo, corso Tukory 129, 90134 Palermo, Italy.
J Neural Transm (Vienna). 2009 Aug;116(8):995-1005. doi: 10.1007/s00702-009-0207-z. Epub 2009 Mar 17.
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.
神经发生在成人大脑的两个区域，即贯穿侧脑室壁的室下区（SVZ）和海马结构中齿状回（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体的增殖与分化。在本综述中，我们研究了由成纤维细胞生长因子2（FGF-2）及其受体（FGFRs）介导的、与成年大鼠脑SVZ和SGZ神经发生相关的营养系统的细胞和功能方面。在SVZ中，FGF-2在SVZ的GFAP阳性细胞中表达，但在增殖的前体细胞中不存在，增殖的前体细胞反而表达FGFR-1和FGFR-2，但不表达FGFR-3 mRNA，尽管FGFR-3在SVZ中表达，以及FGFR-4。因此，在SVZ中，FGF-2似乎可能由与前体细胞谱系不同的GFAP阳性细胞释放，并通过容积传递到达增殖的前体细胞。FGFR-1 mRNA也在SGZ中表达，并定位于BrdU标记的前体细胞中，而FGFR-2和FGFR-3 mRNA，尽管在SGZ中表达，但不在增殖的前体细胞内。老年大鼠SVZ和DG中增殖前体细胞与年龄相关的减少已有充分记录，并且有人提出，部分原因可能是生长因子表达水平改变的结果。因此，老年前体细胞可能对生长因子有反应，这表明在衰老过程中，神经元前体细胞增殖的基本成分得以保留，并且在适当刺激后增加神经发生的能力仍然存在。总之，由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龛，促进成体和老年大脑中的神经发生。
