DEVELOPMENT OF DOPAMINERGIC-NEURONS IN THE HUMAN MESENCEPHALON AND IN-VITRO EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR TREATMENT

The origin and development of the mesencephalic dopaminergic (mesDA) n eurons within the substantia nigra were characterized in human embryos from Postconception (PC) Week 5.0 to 12.0. Tyrosine hydroxylase (TH) immunoreactive cells were first demonstrated in the ventral mesencepha lon at PC Week 5.5 next to the ventricular zone. Cell migration and ne urite outgrowth of TH-positive neurons were timed. Early expression of ganglioside(GM1) was demonstrated in developing neurons. Glial fibril lary acidic protein (GFAP) was first observed at PC Week 10.0 instead, after the dopaminergic neurotransmitter phenotype expression. In vitr o complementary information was obtained: TH-positive cells represente d about 3% of the total cell population after a week in culture, based upon accurate anatomical dissection. They tended to form microaggrega tes and to grow in close contact with glial cells. MesDA neuronal expr ession of TH activity was measured by a biochemical microassay. TH-pos itive cells responded to basic fibroblast growth factor (bFGF) both wi th increased TH activity and neuronal survival. bFGF effects were medi ated by the proliferative action on glial cells. Astroglial GFAP-posit ive cells express nerve growth factor-low-affinity receptor in culture . Information on in vitro and in vivo sequences of mesDA neuronal deve lopment and their response to identified neurotrophic molecules may be invaluable for selection of the most appropriate tissue donor age for brain grafting and development of alternative treatment strategies fo r Parkinson's disease. (C) 1994 Academic Press, Inc.