Fibroblast growth factor receptor‐bearing neurons in the CNS: Identification by receptor‐mediated retrograde transport

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Abstract
Neurons that internalize and retrogradely accumulate acidic (aFGF) or basic (bFGF) fibroblast growth factor were identified by autoradiography after injections of 125I‐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.