ROLE OF FGF IN NEURONAL INJURY

University Of Vermont &St Agric College, Burlington VT

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Abstract

DESCRIPTION (adapted from applicant's abstract): Acidic fibroblastic growth factor (FGF1) is a potent neurotrophic factor for most neuronal populations and a mitogen for many nonneuronal cell types. In the adult nervous system, specific neuronal populations express FGF1 in high levels, including motoneurons, basal forebrain cholinergic neurons and substantia nigra dopaminergic neurons. FGF1 lacks a hydrophobic signal peptide sequence, is not sorted to the secretory pathway, and may not be efficiently released from unstimulated healthy neurons. It is our hypothesis that injury causes the release of sufficient amounts of FGF1 to result in the activation of widely expressed transmembrane FGF receptors (FGFRs). This activation then provides autocrine neurotrophic support to damaged neurons and a paracrine activation signal to glial cells adjacent tot he damaged neurons. This hypothesis suggests that FGF1 is of great importance for the maintenance, plasticity and regeneration of motoneurons. Novel tools, including antibodies that specifically recognize the activated form of FGFRs and FGF1 knockout, FGF2 (a close relative of FGF1) knockout and FGF1/FGF2 double knockout mice will be used to test this hypothetical role of FGF1.