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 parts of the nervous system, and has been shown to exhibit neurotrophic activity. Here we show that c-Met, the receptor for HGF, is expressed in developing rat hippocampus, with the highest levels during the first postnatal weeks. To study the function of HGF, hippocampal neurons were prepared from embryonic rats and treated with different HGF concentrations. In these cultures, HGF increased the number of neurons expressing the 28-kDa calcium-binding protein (calbindin D) in a dose-dependent manner. The effect of HGF was larger than that observed with either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), and cotreatment of the cultures with HGF and the 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 neuronal maturation. BDNF and NT-3 stimulated neurite outgrowth of calbindin D neurons to a much smaller degree. In contrast to calbindin D neurons, HGF did 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-immunoreactive 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 neurons in the hippocampus.
Korhonen
L
L
Department of Neuroscience Neurobiology, Uppsala University, Box 587, BMC, S-75123 Uppsala, Sweden.
Sjöholm
U
U
Takei
N
N
Kern
M A
MA
Schirmacher
P
P
Castrén
E
E
Lindholm
D
D
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D064026:Calbindins; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005333:Fetus; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D064026:Calbindins; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met