Brain-derived neurotrophic factor works coordinately with partner molecules to initiate tyrosine hydroxylase expression in striatal neurons.
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 neurotrophic factor (CNTF), were able to elicit barely detectable (10%) levels of TH induction, regardless of the partner molecule used. These studies suggest that aFGF and/or BDNF may work coordinately with partner molecules to initiate TH expression; while a number of factors including, CNTF and GDNF, may be involved in its subsequent modulation.
Du
X
X
Department of Neurology, Hahnemann University, Philadelphia, PA 19102, USA.
Stull
N D
ND
Iacovitti
L
L
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D003342:Corpus Striatum / Q000166:cytology / Q000201:enzymology*; D004298:Dopamine / Q000494:pharmacology; D004357:Drug Synergism; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016220:Fibroblast Growth Factor 1; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine