RECEPTOR-MEDIATED RETROGRADE TRANSPORT IN CNS NEURONS AFTER INTRAVENTRICULAR ADMINISTRATION OF NGF AND GROWTH-FACTORS

FERGUSON, IA; SCHWEITZER, JB; Bartlett, PF; Johnson, EM

Author(s): FERGUSON, IA; SCHWEITZER, JB; Bartlett, PF; Johnson, EM;
Details: Publication Year 1991-11-22,Volume 313,Issue #4,Page 680-692
Journal Title: JOURNAL OF COMPARATIVE NEUROLOGY
Publication Type: Journal Article
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 (I-125-NGF), substantial amounts of radioactivity had penetrated the ventricular wall surfaces; this binding was transient and nonspecific. The I-125-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 I-125-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 I-125-IGF-II and I-125-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.
Publisher: WILEY-LISS
Keywords: CENTRAL-NERVOUS-SYSTEM; FACTOR PROMOTES SURVIVAL; ADULT-RAT BRAIN; FACTOR-II; CHOLINERGIC NEURONS; ALZHEIMERS-DISEASE; NEURITE FORMATION; MESSENGER-RNA; INSULIN; LOCALIZATION
Publisher's Version: https://doi.org/10.1002/cne.903130411
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Creation Date: 1991-11-22 12:00:00