title: Receptor-mediated retrograde transport in CNS neurons after intraventricular administration of NGF and growth factors.
abstract: Radiolabel tracer techniques were used to follow the distribution of nerve growth factor (NGF) and other neuromodulatory factors after intraventricular injection. Autoradiography showed that shortly after intraventricular injection of radio-iodinated NGF (125I-NGF), substantial amounts of radioactivity had penetrated the ventricular wall surfaces; this binding was transient and nonspecific. The 125I-NGF was progressively cleared from the central nervous system (CNS), presumably via the flow of cerebrospinal fluid (CSF) into the blood. A relatively small proportion of the injected 125I-NGF was taken up by NGF receptor-positive neurons in the CNS. Retrograde accumulation of radiolabel was observed within the basal forebrain cholinergic neurons at 5 hours after intraventricular injection. Labeling intensity was maximal at 18 hours and much reduced by 30 hours. This labeling was blocked by co-injection of an excess of unlabeled NGF. Specific and saturable retrograde labeling was also observed within other NGF receptor-bearing neurons, including the prepositus hypoglossal nucleus and the raphe obscurus nucleus. When epidermal growth factor (EGF), transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, leukemia inhibitory factor (LIF), insulin-like growth factor-I (IGF-I), or IGF-II was radiolabeled and injected intraventricularly, specific labeling of neurons was observed for 125I-IGF-II and 125I-LIF within separate subpopulations of the dorsal and medial raphe. No retrograde accumulation within neurons was observed for EGF, TGF-beta 1, PDGF-AA, PDGF-BB, or IGF-I. This study describes an in vivo method for identifying putative neuromodulatory factors and their responsive neurons.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: I A
authors.initials: IA
authors.lastname: Ferguson
authors.forename: J B
authors.initials: JB
authors.lastname: Schweitzer
authors.forename: P F
authors.initials: PF
authors.lastname: Bartlett
authors.forename: E M
authors.initials: EM
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001345:Autoradiography; D001692:Biological Transport / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D051379:Mice; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor; D014909:Wheat Germ Agglutinins
chemical_list: D006133:Growth Substances; D007457:Iodine Radioisotopes; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D014909:Wheat Germ Agglutinins