Gonzalez A M, Berry M, Maher P A, Logan A, Baird A
UMDS (Guy's Campus) London, United Kingdom.
Brain Res. 1995 Dec 1;701(1-2):201-26. doi: 10.1016/0006-8993(95)01002-x.
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.
为了协调已发表文献中众多不同的研究结果，我们研究了成体正常大鼠脑中FGF-2和FGFR1免疫反应性及其mRNA的细胞分布。结果证实FGF-2和FGFR1在大鼠脑中广泛分布，不同脑区表达FGF-2和FGFR1 mRNA及蛋白质的模式不同：神经元和非神经元细胞显示出不同的亚细胞分布，且根据其所在区域而有所变化。染色和杂交的强度也因所检查的位点和所涉及的细胞类型而异。星形胶质细胞含有最高水平的FGF-2和FGFR1 mRNA，其细胞核内特征性地含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，它们表达FGFR1 mRNA。在这些细胞中，免疫反应性FGFR1主要与神经元纤维的髓鞘相关。在脑室系统中，室管膜细胞合成并含有免疫反应性FGFR1。相比之下，仅第三脑室侧壁的细胞表达FGF-2 mRNA。室管膜下细胞含有高水平的FGF-2和FGFR1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，特定的神经元群体，如海马体的CA2区，显示出高水平的FGF-2 mRNA，其细胞核呈强免疫阳性。同样，高水平的FGFR1 mRNA定位于特定的神经元群体（如杏仁核）。FGFR1免疫反应性主要与有髓纤维束（如纹状体）相关，一些神经元在核周体（如海马体）、细胞核（如中脑三叉神经核）或轴突投射（如下丘脑）中显示免疫反应性。值得注意的是，在许多研究区域中，FGF-2和FGFR1 mRNA和/或其翻译的蛋白质在神经元中（如新皮层）甚至在大脑的同一区域中（如黑质）并不共定位。在其他情况下，FGF-2和FGFR1的mRNA共定位（如视上核）。与外周组织相比，大脑含有高水平的FGF-2，并在正常生理条件下积极表达其基因。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分布，支持了其在正常生理条件下在中枢神经系统中发挥多功能作用的观点。通过关联FGF-2及其高亲和力受体之一FGFR1在中枢神经系统中的定位和合成，应该有可能更好地理解FGF-2在正常和病理条件下的作用。
