EFFECTS OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON NEURONAL STRUCTURE OFDOPAMINERGIC-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 abilit y to influence neuronal structure of dopaminergic neurons in dissociat ed cultures of human fetal ventral mes encephalon after 7 days in vitr o. Following immunocytochemical staining for tyrosine hydroxylase, all surviving dopaminergic neurons were counted. Computer-assisted three- dimensional reconstructions of uniform randomly selected neurons cultu red 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%. M ean soma profile area was significantly enlarged by 18% in BDNF-treate d 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 increas ed by 60%, 125% and 129%, respectively, and the mean number of segment s per cell was increased by 41%. A change in neurite complexity in BDN F-treated cultures was further confirmed by the Shell's concentric sph ere analysis. These results demonstrate that BDNF promotes development and differentiation of human fetal dopaminergic neurons in vitro.