Ferguson I A, Johnson E M
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Comp Neurol. 1991 Nov 22;313(4):693-706. doi: 10.1002/cne.903130412.
Neurons that internalize and retrogradely accumulate acidic (aFGF) or basic (bFGF) fibroblast growth factor were identified by autoradiography after injections of 125 I-aFGF or 125I-bFGF into the adult rat central nervous system (CNS). Neuronal cell bodies within the lateral hypothalamus, pedunculpontine tegmental nucleus, laterodorsal tegmental nucleus, and the paracentral dorsal tegmental nucleus accumulated 125I-aFGF. Neurons in the hippocampus, subiculum, the centrolateral, paracentral, central medial, and parafascicular thalamic nuclei, the supramammillary nucleus, and substantia nigra compacta accumulated 125I-bFGF. The pattern of neuronal labeling with 125I-bFGF in adult rats was similar to that observed in newborn guinea pigs. No 125I-FGF labeling was observed in nerve growth factor (NGF) receptor-bearing neurons, including the basal forebrain cholinergic neurons. Time-course studies indicate that 125I-FGF was internalized at the terminals and retrogradely transported to the neuronal cell bodies. Neurons were retrogradely labeled either by injection of 125I-bFGF into the lateral ventricle or by injection into innervated target tissues. Co-injection of a 250-fold excess of unlabeled FGF with the 125I-FGF abolished the neuronal labeling. Co-injection of wheat germ agglutinin (WGA), which nonspecifically blocks binding of 125I-bFGF to its receptor, also prevented neuronal labeling. These studies demonstrate that specific neuronal populations within the CNS express functional receptors for aFGF and/or bFGF; in these neurons, aFGF and/or bFGF bind specifically to these receptors, are internalized and retrogradely transported to the neuronal soma in a manner analogous to NGF. The data indicate that FGF can provide trophic support to CNS neurons by both direct and indirect mechanisms.
在将125I - aFGF或125I - bFGF注射到成年大鼠中枢神经系统（CNS）后，通过放射自显影鉴定出内化并逆行积累酸性（aFGF）或碱性（bFGF）成纤维细胞生长因子的神经元。下丘脑外侧、脚桥被盖核、背外侧被盖核和中央旁背侧被盖核内的神经元细胞体积累了125I - aFGF。海马、下托、丘脑中央外侧核、中央旁核、中央内侧核和束旁核、乳头体上核以及黑质致密部的神经元积累了125I - bFGF。成年大鼠中125I - bFGF标记神经元的模式与新生豚鼠中观察到的相似。在包括基底前脑胆碱能神经元在内的表达神经生长因子（NGF）受体的神经元中未观察到125I - FGF标记。时间进程研究表明，125I - FGF在终末被内化并逆行运输到神经元细胞体。通过将125I - bFGF注射到侧脑室或注射到受支配的靶组织中，神经元被逆行标记。将250倍过量的未标记FGF与125I - FGF共同注射可消除神经元标记。共同注射小麦胚凝集素（WGA），其非特异性地阻断125I - bFGF与其受体的结合，也可防止神经元标记。这些研究表明，CNS内特定的神经元群体表达aFGF和/或bFGF的功能性受体；在这些神经元中，aFGF和/或bFGF特异性结合这些受体，被内化并以类似于NGF的方式逆行运输到神经元胞体。数据表明，FGF可通过直接和间接机制为CNS神经元提供营养支持。
