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成年幼鼠和老年大鼠脑内神经源性和非神经源性区域星形胶质细胞中纤维母细胞生长因子受体2(FGFR - 2)免疫反应性的细胞结构

Cytoarchitecture of fibroblast growth factor receptor 2 (FGFR-2) immunoreactivity in astrocytes of neurogenic and non-neurogenic regions of the young adult and aged rat brain.

作者信息

Chadashvili Tamuna, Peterson Daniel A

机构信息

Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, Chicago, Illinois 60064, USA.

出版信息

J Comp Neurol. 2006 Sep 1;498(1):1-15. doi: 10.1002/cne.21009.

Abstract

Fibroblast growth factors (FGFs) are polypeptides that exert diverse biological effects on many cell types and tissues during embryogenesis and adulthood. In the adult brain, FGF-2 is primarily expressed by astrocytes and select groups of neurons. It has been shown that FGF-2 is neuroprotective and can stimulate proliferation of NSCs in neurogenic regions of the adult mammalian brain. Cellular responses to FGFs are mediated through membrane-spanning tyrosine kinase receptors in conjunction with low affinity binding to heparin sulfate proteoglycans. Four FGF receptors (FGFR1-4) have been cloned and characterized to date. In this study, we describe the anatomical distribution of FGFR-2 in young and aged rat brains. We demonstrate that the olfactory bulb, hippocampus, and cerebellum display the most robust FGFR-2 expression and observed age-related decrease in FGFR-2 levels in some but not all brain regions. In addition, we identified astrocytes as the primary source of FGFR-2 expression using immunofluorescence confocal microscopy. The astrocyte populations in the neurogenic areas, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the dentate gyrus, express high levels of FGFR-2 protein, which points to its possible involvement in neurogenesis. We also explored the role of FGFR-2 in response to perforant pathway lesion and observed enhanced FGFR-2 expression by astrocytes surrounding the lesion. Thus, FGF-2 biological effects on astrocytes appear to be mediated through FGFR-2-dependent mechanisms, and this may provide an indirect route by which FGF-2 acts on neuronal populations.

摘要

成纤维细胞生长因子(FGFs)是一类多肽,在胚胎发育和成年期对多种细胞类型和组织发挥多种生物学作用。在成年大脑中,FGF-2主要由星形胶质细胞和特定的神经元群体表达。研究表明,FGF-2具有神经保护作用,并且能够刺激成年哺乳动物大脑神经发生区域的神经干细胞增殖。细胞对FGFs的反应是通过跨膜酪氨酸激酶受体介导的,同时与硫酸乙酰肝素蛋白聚糖存在低亲和力结合。迄今为止,已克隆并鉴定了四种FGF受体(FGFR1-4)。在本研究中,我们描述了FGFR-2在幼年和老年大鼠大脑中的解剖分布。我们证明嗅球、海马体和小脑显示出最强的FGFR-2表达,并且在一些但并非所有脑区观察到FGFR-2水平随年龄增长而下降。此外,我们使用免疫荧光共聚焦显微镜确定星形胶质细胞是FGFR-2表达的主要来源。神经发生区域、脑室下区(SVZ)和齿状回颗粒下区(SGZ)的星形胶质细胞群体表达高水平的FGFR-2蛋白,这表明其可能参与神经发生。我们还探讨了FGFR-2在对穿通通路损伤反应中的作用,并观察到损伤周围星形胶质细胞的FGFR-2表达增强。因此,FGF-2对星形胶质细胞的生物学作用似乎是通过FGFR-2依赖性机制介导的,这可能为FGF-2作用于神经元群体提供一条间接途径。

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