Fibroblast growth factor receptor-bearing neurons in the CNS: identification by receptor-mediated retrograde transport.
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.
Ferguson
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IA
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Johnson
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EM
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006168:Guinea Pigs; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D008297:Male; D008636:Mesencephalon / Q000502:physiology; D009474:Neurons / Q000737:chemistry*; D016548:Prosencephalon / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor; D012249:Rhombencephalon / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology
D007457:Iodine Radioisotopes; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors