PMID- 17711418 OWN - NLM STAT- MEDLINE DCOM- 20071120 LR - 20220309 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 103 IP - 2 DP - 2007 Oct TI - Robust stimulation of TrkB induces delayed increases in BDNF and Arc mRNA expressions in cultured rat cortical neurons via distinct mechanisms. PG - 626-36 AB - In cultures of rat cortical neurons, we found that stimulation of tyrosine receptor kinase B (TrkB) with brain-derived neurotrophic factor (BDNF) induced a biphasic expression of BDNF exon IV-IX mRNA, which became obvious 1-3 h (primary induction) and 24-72 h (delayed induction) after the stimulation, and characterized the delayed induction in relation to the mRNA expression of activity-regulated cytoskeleton-associated protein (Arc). Withdrawal of BDNF from the medium after stimulation for 3 h allowed the delayed induction, which was caused at the transcriptional level and dependent upon the initial contact between exogenously added BDNF and TrkB, the effect of which was time- and dose-dependent. The primary induction was controlled by the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) whereas the secondary induction by the calcium (Ca(2+)) signaling pathway. The enhanced Arc or Zif268 mRNA expression was controlled by activation of the ERK/MAPK pathway, both of which were repressed by blocking the binding of endogenously synthesized BDNF to TrkB. Thus, robust stimulation of TrkB autonomously induces delayed BDNF mRNA expression in an activity-dependent manner in rat cortical neurons, resulting in the stimulation of Arc mRNA expression through endogenously synthesized BDNF, the process being orchestrated by the Ca(2+) and ERK/MAPK signaling pathways. FAU - Yasuda, Makoto AU - Yasuda M AD - Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan. FAU - Fukuchi, Mamoru AU - Fukuchi M FAU - Tabuchi, Akiko AU - Tabuchi A FAU - Kawahara, Masahiro AU - Kawahara M FAU - Tsuneki, Hiroshi AU - Tsuneki H FAU - Azuma, Yuko AU - Azuma Y FAU - Chiba, Yusuke AU - Chiba Y FAU - Tsuda, Masaaki AU - Tsuda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070817 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Culture Media, Serum-Free) RN - 0 (Cytoskeletal Proteins) RN - 0 (DNA, Complementary) RN - 0 (Indicators and Reagents) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (activity regulated cytoskeletal-associated protein) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Cells, Cultured MH - Culture Media, Serum-Free MH - Cytoskeletal Proteins/*biosynthesis MH - DNA, Complementary/biosynthesis/genetics MH - Extracellular Signal-Regulated MAP Kinases/biosynthesis/genetics/metabolism MH - Genes, Immediate-Early/drug effects MH - Immunoblotting MH - Indicators and Reagents MH - Luciferases/genetics MH - Nerve Tissue Proteins/*biosynthesis MH - Neurons/drug effects/*metabolism MH - Phosphorylation MH - RNA, Messenger/*biosynthesis MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/*agonists MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/drug effects MH - Transcriptional Activation/drug effects MH - Transfection EDAT- 2007/08/23 09:00 MHDA- 2007/12/06 09:00 CRDT- 2007/08/23 09:00 PHST- 2007/08/23 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2007/08/23 09:00 [entrez] AID - JNC4851 [pii] AID - 10.1111/j.1471-4159.2007.04851.x [doi] PST - ppublish SO - J Neurochem. 2007 Oct;103(2):626-36. doi: 10.1111/j.1471-4159.2007.04851.x. Epub 2007 Aug 17.