Effect of FGF-9 on cultured neurons : novel approach for the treatment of neurodegenerative disorders

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We examined the effect of fibroblast growth factor (FGF)-9 on primary cultures of rat basal forebrain cholinergic neurons (BFCN) obtained at embryonic day 17 and anterior horn cholinergic neurons (AHCN) obtained embryonic day 14. FGF-9 enhanced survival of AChE-positive neurons, increased their mean soma size, and upregulated choline their acetyltransferase (ChAT) activity in BFCN and AHCN.For BFCN, The ChAT-promoting effect of FGF-9 was approximately as potent as that of nerve growth factor (NGF) and was greater than those of basic fibroblast growth factor (bFGF), ciliary neurotrophic factor (CNTF), or glia-derived neurotrophic factor (GDNF). Simultaneous addition of FGF-9 and NGF induced extremely high ChAT levels, suggesting that FGF-9 and NGF may enhance cholinergic properties in BFCN via different pathways that can act synergistically. In immunocytochemical and in situ hybridization studies in cultured cells and also in sections of adult rat brain, BFCN showed cytoplasmic immunostaining for FGF-9 and expressed FGF-9 messenger RNA ; thus, we concluded that FGF-9 acts on BFCN in an autocrine and/or paracrine manner. Thus, we conclude that FGF-9 may be a promising candidate for therapeutic trials in Alzheimer disease and amyotrophic lateral sclerosis.The next step is to develop effective methods to deliver exogenous FGF-9 into the central nervous system. We coupled FGF-9 with some polyamines and this FGF-9-polyamine complex can pass through in vitro BBB system ; however, the neurotrophic effect of FGF-9 on BFCN or AHCN was somewhat diminished after coupling with polyamine. Experiments to establish optimal condition for FGF-9-polyamine coupling are now underway.