Induction of tyrosine hydroxylase gene expression in human foetal cerebral cortex

Human foetal cerebral cortex (9-14 weeks gestational age) was dissected out and cultured in microwell plates. It was then treated with brain-derived neurotrophic factor (BDNF, 50 ng/ml), dopamine (10 mM) or their combination. After 5 weeks of this treatment tyrosine hydroxylase (TH)-immunopositive neurones were detected at a level of 0.73% of total neurones present. This represented 300-500 TH + neurones per microwell. None were seen in untreated cultures. This correlates with induction of the entire dopaminergic phenotype in foetal rat cerebral cortex (E1214) by the same co-treatment applied for a much shorter time period (7 days), which implies that the complete dopaminergic phenotype is also induced in cultured human foetal tissue over a longer period, reflecting the 5-fold longer neuronal gestational period.