FIBROBLAST GROWTH-FACTORS - STRUCTURE-ACTIVITY ON DOPAMINE NEURONS IN-VITRO

We investigated the effect of neurotrophic factors on dopamine (DA) ce lls in vitro. At concentrations of nanograms/c.c. basic fibroblast gro wth factor (bFGF) is a more potent DA-trophic agent than brain derived neurotrophic factor (BDNF) or epidermal growth factor (EGF) in fetal mid brain neurons. In these cells, bFGF produces a greater increase of DA levels and percentage of cells positive for tyrosine hydroxylase ( TH+) than BDNF and EGF. Acidic fibroblast growth factor (aFGF) was not tested in fetal DA cells since aFGF requires heparin for its effect a nd fetal mid brain cultures do not grow well in the presence of a high concentration of heparin. We further investigated the effect of bFGF and aFGF, and two of their analogs, in catecholamine rich human neurob lastoma cells NB69. In these cells aFGF, at concentrations of picogram s/c.c., increases DA levels, while its analogs, E118 and super short, have no effect. Acidic FGF also increases norepinephrine levels, the n umber of TH+ cells, and the percentage of TH+ with respect to the tota l number of nuclei. Basic fibroblast growth factor (bFGF) produced sim ilar, but less potent effects. Acidic FGF was active only in the prese nce of heparin; the effect of bFGF was independent of heparin. FGFs ar e promising drugs for the treatment of PD, though further investigatio ns with these compounds should be performed before their use in clinic al trials.