Effects of brain-derived neurotrophic factor on neuronal structure of dopaminergic neurons in dissociated cultures of human fetal mesencephalon.

Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of cultured fetal mesencephalic dopaminergic neurons of rat and human origin. In the present study, BDNF was tested for its ability to influence neuronal structure of dopaminergic neurons in dissociated cultures of human fetal ventral mesencephalon after 7 days in vitro. Following immunocyto chemical staining for tyrosine hydroxylase, all surviving dopaminergic neurons were counted. Computer-assisted three-dimensional reconstructions of uniform randomly selected neurons cultured with 50 ng/ml BDNF (n = 120) or without BDNF (n = 80) were made. BDNF increased the number of surviving human dopaminergic neurons by 76%. Mean soma profile area was significantly enlarged by 18% in BDNF-treated neurons as compared to controls. Analysis of parameters of neuritic size and complexity in these cultures revealed that combined neuritic length, combined neuritic volume, and neuritic field area were increased by 60%, 125% and 129%, respectively, and the mean number of segments per cell was increased by 41%. A change in neurite complexity in BDNF-treated cultures was further confirmed by the Sholl's concentric sphere analysis. These results demonstrate that BDNF promotes development and differentiation of human fetal dopaminergic neurons in vitro.