NEUROTROPHIC EFFECT OF HEPATOCYTE GROWTH-FACTOR ON CENTRAL-NERVOUS-SYSTEM NEURONS IN-VITRO

Although the expression of hepatocyte growth factor (HGF) and its rece ptor, proto-oncogene c-met, has been demonstrated in the central nervo us system (CNS), the function of HGF in the CNS was not fully understo od, In the present studies, we determined the effects of HGF on neuron al development in neocortical explant and mesencephalic neurons obtain ed from embryonic rat brain, HGF clearly enhanced neurite outgrowth in neocortical explants, In the mesencephalic culture, the number of tyr osine hydroxylase (TH)-positive neurons was significantly higher in th e HGF-treated wells and the neurites of the TH-positive neurons appear to be more developed, Moreover, the dopamine uptake into mesencephali c neurons was also enhanced by HGF treatment, indicating that HGF prom otes the survival and/or maturation of mesencephalic dopaminergic neur ons, In both neocortical explants and mesencephalic neurons, c-met aut ophosphorylation was induced by HGF and MAP kinase activation was also detected in the neocortical explant, Furthermore, Western blot analys is of the cultured CNS cells revealed that HGF was expressed mainly in microglia, These results suggest that HGF from microglia has neurotro phic activity on the CNS neurons and plays significant roles in the de velopment of the CNS. (C) 1996 Wiley-Liss, Inc.