A COMPREHENSIVE ANALYSIS OF THE DISTRIBUTION OF FGF-2 AND FGFR1 IN THE RAT-BRAIN

A COMPREHENSIVE ANALYSIS OF THE DISTRIBUTION OF FGF-2 AND FGFR1 IN THE RAT-BRAIN
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DOI:
10.1016/0006-8993(95)01002-x
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发表时间:
1995-12-01
期刊:
影响因子:
2.9
通讯作者:
BAIRD, A
BAIRD, A
中科院分区:
医学3区
文献类型:
--
作者:
GONZALEZ, AM;BERRY, M;BAIRD, A

文献摘要

被引文献

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我们研究了FGF-2和FGFR 1免疫反应性及其mRNA在整个正常成年大鼠大脑中的细胞分布,以调和已发表文献中的许多不同发现。结果证实了FGF-2和FGFR 1在大鼠脑中的广泛分布,并且不同区域表达FGF-2和FGFR 1 mRNA和蛋白质的不同模式:神经元和非神经元细胞显示出不同的亚细胞分布,这些分布根据它们所处的区域而变化。染色和杂交的强度也根据所检查的基因座和所涉及的细胞类型而变化。星形胶质细胞含有最高水平的FGF-2和FGFR 1 mRNA,并且典型地,在细胞核内具有高水平的免疫反应性FGF-2。在非神经元细胞中,少突胶质细胞不合成或含有显著水平的FGF-2免疫反应性,然而,它们确实表达FGFR 1 mRNA。在这些细胞中,免疫反应性FGFR 1主要与神经纤维的髓鞘相关。在心室系统中,室管膜细胞合成并含有免疫反应性FGFR 1。相比之下,只有衬在心室侧壁的细胞表达FGF-2 mRNA。室管膜下细胞含有高水平的FGF-2和FGFR 1免疫反应性,神经元表达低水平的FGF-2 mRNA,免疫反应性FGF-2主要定位于核周体。然而,选定的神经元群体,如海马的CA 2区,显示高水平的FGF-2 mRNA,其中细胞核是强免疫阳性的。类似地,高水平的FGFR 1 mRNA定位于选定的神经元群体(例如杏仁核)。FGFR 1免疫反应性主要与有髓纤维束(例如纹状体)相关,并且一些神经元在核周体(例如海马)、核(例如中脑三叉神经核)或轴突投射(例如下丘脑)中显示免疫反应性。值得注意的是,在所研究的许多区域中,FGF-2和FGFR 1 mRNA和/或其翻译的蛋白不在神经元(例如新皮质)中共定位,甚至不在大脑的相同区域(例如黑质)中共定位。在其他情况下,FGF-2和FGFR 1的mRNA共定位(例如视上核)。与外周组织相比,脑含有高水平的FGF-2,并在正常生理条件下主动表达其基因。免疫反应性FGF-2在神经元和非神经元脑细胞中的高度特异性解剖学分布支持其在正常生理学下在CNS中起多功能作用的观点。通过将FGF-2及其高亲和力受体之一FGFR 1在CNS中的定位和合成相关联,应该可以更好地理解FGF-2在正常和病理条件下的作用。
We have examined the cellular distribution of both FGF-2 and FGFR1 immunoreactivity and their mRNAs throughout the normal adult rat brain in order to reconcile numerous disparate findings in the published literature. The results confirm a widespread distribution of FGF-2 and FGFR1 in the rat brain, and different regions express distinct patterns of FGF-2 and FGFR1 mRNA and protein: neuronal and non-neuronal cells show different subcellular distributions that vary according to the area where they are located. The intensity of the staining and hybridization also varies according to the loci examined and the cell type involved. Astrocytes contain the highest levels of FGF-2 and FGFR1 mRNAs, and characteristically, possess high levels of immunoreactive FGF-2 within the nucleus. Amongst non-neuronal cells, oligodendrocytes do not synthesize or contain significant levels of FGF-2 immunoreactivity however, they do express FGFR1 mRNA. In these cells, immunoreactive FGFR1 is mainly associated with the myelin sheaths of neuronal fibers. In ventricular systems, ependymal cells synthesize and contain immunoreactive FGFR1. In contrast, only cells lining the lateral wall of the IIIrd ventricle express FGF-2 mRNA. Subependymal cells contain high levels of both FGF-2 and FGFR1 immunoreactivity.Neurons express low levels of FGF-2 mRNA and immunoreactive FGF-2 is localized predominantly to the perikaryon. However, selected populations of neurons, such as CA2 field of the hippocampus, show high levels of FGF-2 mRNA, in which the nucleus is strongly immunopositive, Similarly, high levels of FGFR1 mRNA are localized to select populations of neurons (e.g. amygdala). FGFR1 immunoreactivity is mainly associated with myelinated fiber tracts (e.g. striatum), and some neurons show immunoreactivity in the perikaryon (e.g. hippocampus), the nucleus (e.g. mesencephalic trigeminal nucleus), or in axonal projections (e.g. hypothalamus). Remarkably, in many of the areas studied, FGF-2 and FGFR1 mRNA and/or their translated protein do not co-localize in neurons (e.g. neo-cortices) or even in the same regions of the brain (e.g. substantia nigra). In other instances, mRNAs for both FGF-2 and FGFR1 colocalize (e.g. supraoptic nucleus).The brain, in contrast to peripheral tissues, contains high levels of FGF-2 and actively expresses its gene under normal physiological conditions. The highly specific anatomical distribution of immunoreactive FGF-2 in neuronal and non-neuronal brain cells, supports the notion that it plays a multifunctional role in the CNS under normal physiology. By correlating the localization and the synthesis of FGF-2 and one of its high affinity receptors, FGFR1, in the CNS, it should be possible to obtain a better understanding of the roles of FGF-2 in normal and pathological conditions.