Brain-derived neurotrophic factor works coordinately with partner molecules to initiate tyrosine hydroxylase expression in striatal neurons

Brain Research
X DuL Iacovitti

Abstract

Previous studies demonstrated that the cooperative interaction of acidic fibroblast growth factor (aFGF) and a partner molecule could induce the novel expression of the catecholamine (CA) biosynthetic enzyme, tyrosine hydroxylase (TH) in striatal neurons [Du and Iacovitti, J. Neurosci., in press; Du et al., J. Neurosci., 14 (1994) 7688-7694; Iacovitti et al., submitted]. The present study demonstrates that in addition to aFGF, brain-derived neurotrophic factor (BDNF) is also capable of moderate levels of TH induction (30% TH+ striatal neurons) when administered at high concentrations (100 ng/ml). As with aFGF, BDNF's activity depended on its coupling to an appropriate partner molecule; the most potent of which were 10 microM dopamine (DA) and 50 microM mazindol. BDNF + DA-induced TH expression was first evident after at 12 h; peaked by 18 h and declined by 4 days in culture. Cyclohexamide eliminated nearly all and alpha-amanitin reduced by half the TH induction elicited by DA and BDNF; indicating that both de novo transcription and translation were required for increased expression. In contrast with aFGF and BDNF, other putative dopamine differentiation factors, such as glial-derived neurotrophic factor (GDNF) and ciliary neuro...Continue Reading

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