Department of Experimental Biomedicine and Clinical Neuroscience, div. Human Physiology, Laboratory of Molecular Neurobiology, University of Palermo, corso Tukory 129, IT-90134 Palermo, Italy.
Brain Res. 2010 Oct 28;1358:39-45. doi: 10.1016/j.brainres.2010.08.083. Epub 2010 Sep 18.
It is largely accepted that neurogenesis in the adult brain decreases with age and reduced levels of local neurotrophic support is speculated to be a contributing factor. Among neurotrophic factors involved on neurogenesis, we focused our attention on the neurotrophic system fibroblast growth factor-2 (FGF-2) and its receptor FGFR1, a potent modulator of precursor cell proliferation. In the present work, we aimed to analyse if potential age-dependent changes of the FGF-2/FGFR1 neurotrophic system may give account for the age-dependent decline of precursor cell proliferation in the neurogenic region of the subventricular zone (SVZ) in the rat brain. Using in situ hybridization and western blotting procedures we examined FGF-2 and FGFR1 expression levels in the SVZ of 20-month-old rats as compared to young adult 3-month-old rats. The results showed that during aging the FGF-2 and its receptor expression levels, both as mRNA and protein, were unchanged in the SVZ. The levels of phosphorylated FGFR1 form did not show significant variations suggesting that also the level of receptor activation does not change during aging. No changes were also observed in the phosphorylation of two FGFR1 related proteins involved in intracellular signaling, the canonical extracellular signal-regulated kinase Erk1/2 and the phospholipase-Cγ1. Additionally, we could show that also the proliferation rate of stem cells does not change during aging. Taken together, our results show that FGF-2/FGFR1 neurotrophic system expression level and its basal activation do not account for the age-dependent decline of precursor cell proliferation in the rat brain.
人们普遍认为，成年人大脑中的神经发生随着年龄的增长而减少，并且局部神经营养支持水平降低被认为是一个促成因素。在涉及神经发生的神经营养因子中，我们将注意力集中在神经发生的神经营养因子纤维母细胞生长因子-2（FGF-2）及其受体 FGFR1 上，这是前体细胞增殖的有力调节剂。在本工作中，我们旨在分析 FGF-2/FGFR1 神经营养系统的潜在年龄依赖性变化是否可以解释大鼠脑侧脑室下区（SVZ）神经发生区前体细胞增殖随年龄增长的下降。通过原位杂交和 Western blot 程序，我们检查了 20 个月大的大鼠 SVZ 中的 FGF-2 和 FGFR1 表达水平，与年轻成年 3 个月大的大鼠进行比较。结果表明，在衰老过程中，SVZ 中的 FGF-2 及其受体表达水平（无论是 mRNA 还是蛋白质）均未发生变化。磷酸化 FGFR1 形式的水平没有显示出明显的变化，表明受体激活水平在衰老过程中也没有变化。两种参与细胞内信号转导的 FGFR1 相关蛋白，即经典细胞外信号调节激酶 Erk1/2 和磷脂酶-Cγ1 的磷酸化也没有变化。此外，我们还表明，干细胞的增殖率在衰老过程中也没有变化。综上所述，我们的结果表明，FGF-2/FGFR1 神经营养系统的表达水平及其基础激活并不能解释大鼠脑前体细胞增殖随年龄增长的下降。
