PLASMINOGEN PROMOTES THE DEVELOPMENT OF RAT MESENCEPHALIC DOPAMINERGIC-NEURONS IN-VITRO

In order to investigate the physiological significance of plasminogen, which is produced by and secreted from microglia, we determined the effects of plasminogen on the development of primary cultured mesencephalic neurons from 16-day-old embryonic rats. Plasminogen markedly increased dopamine uptake and the dopamine content of cultured neurons. Furthermore, the number of mesencephalic dopaminergic neurons, which was determined by immunostaining with tyrosine hydroxylase antibody, was significantly increased in the presence of plasminogen. However, plasminogen had only a slight effect on gamma-aminobutyric acid (GABA) uptake and glutamic acid decarboxylase activity in mesencephalic neurons. The effect on dopaminergic neurons was also observed in the culture in the presence of cytosine arabinoside. In addition, plasminogen had no effect on the number of glial fibrillary acidic protein-positive cells. These results suggest that plasminogen acts directly on neurons and enhances the development of dopaminergic neurons in a rather selective manner.