Expression of c-Met in developing rat hippocampus: evidence for HGF as a neurotrophic factor for calbindin D-expressing neurons

Hepatocyte growth factor-scatter factor (HGF) is expressed in different par ts of the nervous system, and has been shown to exhibit neurotrophic activi ty. Here we show that c-Met, the receptor for HGF, is expressed in developi ng rat hippocampus, with the highest levels during the first postnatal week s. To study the function of HGF, hippocampal neurons were prepared from emb ryonic rats and treated with different HGF concentrations. In these culture s, HGF increased the number of neurons expressing the 28-kDa calcium-bindin g protein (calbindin D) in a dose-dependent manner. The effect of HGF was l arger than that observed with either brain-derived neurotrophic factor (BDN F) or neurotrophin-3 (NT-3), and cotreatment of the cultures with HGF and t he neurotrophins was additive with respect to calbindin D neurons. Besides affecting the number of neurons, HGF significantly increased the degree of sprouting of calbindin D-positive neurons, suggesting an influence on neuro nal maturation. BDNF and NT-3 stimulated neurite outgrowth of calbindin D n eurons to a much smaller degree. In contrast to calbindin D neurons, HGF di d not significantly increase the number of neurons immunoreactive with the neurotransmitter gamma-aminobutyric acid (GABA) in the hippocampal cultures . Immunohistochemical studies showed that c-Met-, calbindin D- and HGF-immu noreactive cells are all present in the dentate gyrus and partly colocalize within neurons. These results show that HGF acts on calbindin D-containing hippocampal neurons and increases their neurite outgrowth, suggesting that HGF plays an important role for the maturation and function of these neuro ns in the hippocampus.