Weickert C S, Kittell D A, Saunders R C, Herman M M, Horlick R A, Kleinman J E, Hyde T M
Neuropathology Section, Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1385, USA.
Neuroscience. 2005;131(1):219-33. doi: 10.1016/j.neuroscience.2004.09.070.
Basic fibroblast growth factor (bFGF) is an important mitogen and neurotrophic factor that binds and signals through the high-affinity receptor, fibroblast growth factor receptor 1 (FGFR1). However, only a limited amount of information is available concerning the molecular forms and anatomical distribution of fibroblast growth factors (FGFs) in the normal human brain. We found multiple bFGF and FGFR1 mRNA transcripts which vary in expression pattern across human brain regions. Using in situ hybridization and immunohistochemistry, we localized bFGF and FGFR1 mRNA and protein to cells in the normal adult human hippocampus and caudal entorhinal cortex (ERC). The majority of pyramidal neurons contained FGFR1 mRNA and protein in the mesial temporal lobe, with neurons in the CA2/CA3 region demonstrating the highest levels of FGFR1 mRNA. In contrast to FGFR1, bFGF mRNA expression was detected at very low levels in a small fraction of the neurons in the human hippocampus and caudal ERC. While bFGF mRNA may be expressed at low levels in neurons, bFGF-immunopositive cells with astrocytic features were detected throughout the mesial temporal lobe in rats, monkeys and humans. bFGF immunoreactive processes are found traversing the dentate gyrus, and bFGF immunoreactive cells are found in the neurogenic subgranular zone in all three mammalian species studied. The anatomical distribution of these two FGF family members suggests that bFGF is endogenously positioned to be involved in ongoing neurogenesis in the adult hippocampus, and that FGF trophic signaling to differentiated neurons could involve the release of astrocytic bFGF acting on neuronal FGFR1 in the normal adult human hippocampus.
碱性成纤维细胞生长因子（bFGF）是一种重要的促有丝分裂剂和神经营养因子，它通过高亲和力受体——成纤维细胞生长因子受体1（FGFR1）进行结合并传递信号。然而，关于正常人脑中成纤维细胞生长因子（FGFs）的分子形式和解剖分布，目前可用的信息有限。我们发现了多种bFGF和FGFR1 mRNA转录本，它们在人类脑区的表达模式各不相同。通过原位杂交和免疫组织化学技术，我们将bFGF和FGFR1 mRNA及蛋白定位到正常成年人类海马体和尾侧内嗅皮质（ERC）中的细胞。在颞叶内侧，大多数锥体细胞含有FGFR1 mRNA和蛋白，其中CA2/CA3区域的神经元FGFR1 mRNA水平最高。与FGFR1不同，在人类海马体和尾侧ERC的一小部分神经元中，bFGF mRNA表达水平极低。虽然bFGF mRNA可能在神经元中低水平表达，但在大鼠、猴子和人类的颞叶内侧均检测到具有星形胶质细胞特征的bFGF免疫阳性细胞。在所有研究的三种哺乳动物中，均发现bFGF免疫反应性纤维穿过齿状回，且在神经源性颗粒下区发现bFGF免疫反应性细胞。这两种FGF家族成员的解剖分布表明，bFGF在体内的定位有助于成年海马体中正在进行的神经发生，并且在正常成年人类海马体中，FGF对分化神经元的营养信号传导可能涉及星形胶质细胞释放的bFGF作用于神经元FGFR1。
