PMID- 17506860 OWN - NLM STAT- MEDLINE DCOM- 20070907 LR - 20131121 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 102 IP - 2 DP - 2007 Jul TI - Bdnf gene is a downstream target of Nurr1 transcription factor in rat midbrain neurons in vitro. PG - 441-53 AB - The transcription factor Nurr1 is essential for the generation of midbrain dopaminergic neurons (mDA). Only a few Nurr1-regulated genes have so far been identified and it remains unclear how Nurr1 influences the development and function of dopaminergic neurons. To identify novel Nurr1 target genes we have used genome-wide expression profiling in rat midbrain primary cultures, enriched in dopaminergic neurons, following up-regulation of Nurr1 expression by depolarization. In this study we demonstrate that following depolarization the hyperexpression of Nurr1 and the brain derived neurotrophic factor (BDNF) are phospholipase C- and protein kinase C-dependent. We show that Bdnf, which encodes a neurotrophin involved also in the phenotypic maturation of mDA neurons, is a novel Nurr1 target gene. By RNA interference experiments we show that a decreased Nurr1 expression is followed by tyrosine hydroxylase and BDNF mRNA and protein down-regulation. Reporter gene assay experiments performed on midbrain primary cultures using four Bdnf promoter constructs show that Bdnf is a direct target gene of Nurr1. Taken together, our findings suggest that Nurr1 might also influence the development and the function of midbrain dopaminergic neurons via direct regulation of Bdnf expression. FAU - Volpicelli, Floriana AU - Volpicelli F AD - Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Developmental Neurobiology, Naples, Italy. volpicel@igb.cnr.it FAU - Caiazzo, Massimiliano AU - Caiazzo M FAU - Greco, Dario AU - Greco D FAU - Consales, Claudia AU - Consales C FAU - Leone, Luigi AU - Leone L FAU - Perrone-Capano, Carla AU - Perrone-Capano C FAU - Colucci D'Amato, Luca AU - Colucci D'Amato L FAU - di Porzio, Umberto AU - di Porzio U LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070515 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (DNA-Binding Proteins) RN - 0 (Nr4a2 protein, rat) RN - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Transcription Factors) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.- (Type C Phospholipases) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Cell Differentiation/physiology MH - Cells, Cultured MH - DNA-Binding Proteins/*genetics MH - Dopamine/*metabolism MH - Down-Regulation/physiology MH - Gene Expression Profiling MH - Gene Expression Regulation, Developmental/*physiology MH - Membrane Potentials/genetics MH - Mesencephalon/cytology/embryology/*metabolism MH - Neurons/*metabolism MH - Nuclear Receptor Subfamily 4, Group A, Member 2 MH - Oligonucleotide Array Sequence Analysis MH - Protein Kinase C/metabolism MH - RNA, Messenger/metabolism MH - RNA, Small Interfering MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/genetics MH - Substantia Nigra/embryology/metabolism MH - Transcription Factors/*genetics MH - Type C Phospholipases/metabolism MH - Tyrosine 3-Monooxygenase/genetics/metabolism MH - Up-Regulation/physiology MH - Ventral Tegmental Area/embryology/metabolism EDAT- 2007/05/18 09:00 MHDA- 2007/09/08 09:00 CRDT- 2007/05/18 09:00 PHST- 2007/05/18 09:00 [pubmed] PHST- 2007/09/08 09:00 [medline] PHST- 2007/05/18 09:00 [entrez] AID - JNC4494 [pii] AID - 10.1111/j.1471-4159.2007.04494.x [doi] PST - ppublish SO - J Neurochem. 2007 Jul;102(2):441-53. doi: 10.1111/j.1471-4159.2007.04494.x. Epub 2007 May 15.