Belluardo Natale, Mudo' Giuseppa, Bonomo Alessandra, Di Liberto Valentina, Frinchi Monica, Fuxe Kjell
Department of Experimental Medicine, Division of Human Physiology, Laboratory of Molecular Neurobiology, University of Palermo, corso Tukory 129, 90134 Palermo, Italy.
Brain Res. 2008 Feb 8;1193:12-24. doi: 10.1016/j.brainres.2007.11.069. Epub 2007 Dec 14.
Precursor cell proliferation is present in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus of adult rat and persists during aging although at reduced levels. Previous studies have shown that acute intermittent nicotine treatment significantly increases fibroblast growth factor-2 (FGF-2) expression in several brain regions of aged rats. The aim of the present investigation was to test the hypothesis that nicotine-induced expression of FGF-2 may restore the age-related decline of precursor cell proliferation. It was first demonstrated that nicotine treatment increases both mRNA and protein FGF-2 in the SVZ of aged male rats (18 months old). The effect of nicotine on precursor cell proliferation in the SVZ was studied by i.p. injection of 5-bromo-2'-deoxyuridine (BrdU) 40 mg/kg to label dividing cells. The nicotine treatment was found to significantly enhance precursor cell proliferation in the SVZ. This increase was sufficiently large to restore the age-related decline of proliferating precursor cells observed in aged rats to that found in young adult rats (3 months old). FGF-2 was expressed in GFAP-positive cells and may act via its receptor FGFR1 that was found expressed in nestin-positive cells of the SVZ. The data obtained demonstrated that the age-related decline of precursor cell proliferation may be counteracted by activating a trophic mechanism mediated by FGF-2.
成年大鼠侧脑室室管膜下区（SVZ）和海马齿状回颗粒下区（SGZ）存在前体细胞增殖，且在衰老过程中持续存在，不过水平有所降低。先前的研究表明，急性间歇性尼古丁处理可显著增加老年大鼠多个脑区的成纤维细胞生长因子-2（FGF-2）表达。本研究的目的是检验尼古丁诱导的FGF-2表达可能恢复与年龄相关的前体细胞增殖下降这一假说。首先证明，尼古丁处理可增加老年雄性大鼠（18月龄）SVZ中FGF-2的mRNA和蛋白质水平。通过腹腔注射40 mg/kg的5-溴-2'-脱氧尿苷（BrdU）来标记分裂细胞，研究尼古丁对SVZ中前体细胞增殖的影响。发现尼古丁处理可显著增强SVZ中的前体细胞增殖。这种增加幅度足够大，可将老年大鼠中观察到的与年龄相关的增殖前体细胞下降恢复到年轻成年大鼠（3月龄）的水平。FGF-2在GFAP阳性细胞中表达，并可能通过其在SVZ巢蛋白阳性细胞中表达的受体FGFR1发挥作用。所获得的数据表明，通过激活由FGF-2介导的营养机制，可以抵消与年龄相关的前体细胞增殖下降。
