RESUMO
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.
Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Hipocampo/embriologia , Hipocampo/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Calbindinas , Contagem de Células , Células Cultivadas , Relação Dose-Resposta a Droga , Esquema de Medicação , Feto , Fator de Crescimento de Hepatócito/farmacologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neuritos/ultraestrutura , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Neurotrofina 3/farmacologia , Proteínas Proto-Oncogênicas c-met/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fatores de Tempo , Ácido gama-Aminobutírico/metabolismoRESUMO
Experimental autoimmune encephalomyelitis (EAE) can be induced in resistant BALB/c mice by ultrasound-formed adjuvant emulsion. In contrast to susceptible mouse strains large numbers of neutrophils secreting TNF-alpha occupied the central nervous system (CNS) of BALB/c mice with severe EAE, whereas only small numbers of macrophages and CD4+ T-cells could be detected. CNS infiltration was preceded with activation of microglial cells. Ultrasound formed adjuvant induced early IFN-gamma expression in popliteal lymph nodes of BALB/c mice, whereas conventional adjuvant induced delayed IFN-gamma production. Although the clinical outcome of EAE was similar to that seen in susceptible mice, the pathogenesis was distinct having possible implications on the different forms seen in multiple sclerosis.
