The origin and development of the mesencephalic dopaminergic (mesDA) neurons 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 mesencephalon at PC Week 5.5 next to the ventricular zone. Cell migration and neurite outgrowth of TH-positive neurons were timed. Early expression of ganglioside(GM1) was demonstrated in developing neurons. Glial fibrillary acidic protein (GFAP) was first observed at PC Week 10.0 instead, after the dopaminergic neurotransmitter phenotype expression. In vitro complementary information was obtained: TH-positive cells represented about 3% of the total cell population after a week in culture, based upon accurate anatomical dissection. They tended to form microaggregates and to grow in close contact with glial cells. MesDA neuronal expression of TH activity was measured by a biochemical microassay. TH-positive cells responded to basic fibroblast growth factor (bFGF) both with increased TH activity and neuronal survival. bFGF effects were mediated by the proliferative action on glial cells. Astroglial GFAP-positive cells express nerve growth factor-low-affinity receptor in culture. Information on in vitro and in vivo sequences of mesDA neuronal development 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 for Parkinson's disease.
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