THE STIMULATORY EFFECT OF BRAIN-DERIVED NEUROTROPHIC FACTOR ON DOPAMINERGIC PHENOTYPE EXPRESSION OF EMBRYONIC RAT CORTICAL-NEURONS IN-VITRO

Cells of embryonic (E12-16) rat cerebral cortex were cultured for 7 days in vitro (7DIV) in the presence of either brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), with or without dopamine (DA). Chronic treatment of cells with DA or BDNF alone increased (300% and 600%, respectively) the number of the cells that expressed tyrosine hydroxylase (TH). However, the combination of BDNF and DA treatment greatly increased the expression of TH in E14 cortical cells in a dose-dependent manner, to a much greater extent than DA or BDNF alone. This marked response due to treatment with both BDNF and DA was greater in cortical tissue from E12 embryos than that from E14 embryos. The combination of CNTF and DA also increased expression of the dopaminergic phenotype whilst CNTF alone was ineffective, but this effect was largely due to DA. No effect of DA, or of neurotrophic factors, was observed on cortical cells from E16 embryos under any of the treatment conditions. The present study reveals how chemical environment plays an important role in determining the final phenotype of cortical neurons during early periods in brain development. BDNF, but not CNTF, may influence the differentiation of fetal cortical cells towards a dopaminergic phenotype via a unique mechanism, different from that due to DA. This combination of nerve growth factor and neurotransmitter may be of general importance in phenotype determination in the early developmental stages of the nervous system.