PMID- 26596846 OWN - NLM STAT- MEDLINE DCOM- 20160915 LR - 20151130 IS - 1872-9754 (Electronic) IS - 0197-0186 (Linking) VI - 91 DP - 2015 Dec TI - Self-amplified BDNF transcription is a regulatory system for synaptic maturation in cultured cortical neurons. PG - 55-61 LID - S0197-0186(15)30059-0 [pii] LID - 10.1016/j.neuint.2015.10.009 [doi] AB - Neuronal cell survival and synaptic plasticity are controlled through expression of various neurotrophic factors including brain-derived neurotrophic factor (BDNF). In the present study, we examined the mechanism behind BDNF-induced Bdnf mRNA production and the physiological role of its amplification system using cortical neurons. Exogenous BDNF was applied to the cultured cortical neurons at days in vitro (DIV) 3 and DIV 7 with or without inhibitors for intracellular signaling. Expression levels of total Bdnf and Bdnf variants (exon I, exon IV, and exon VI) were biphasically increased after the BDNF application in different developing stage of neurons. Inhibitor for extracellular signal-regulated kinase, calmodulin dependent protein kinase II, or protein kinase A repressed the BDNF-induced Bdnf mRNA expression. Furthermore, we found that application of TrkB-Fc, which scavenges produced endogenous BDNF, resulted in weakened BDNF/TrkB signaling and decreased expression of postsynaptic proteins, suggesting that newly synthesized BDNF induced by the self-amplification system contributes to the synaptic maturation and function. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Nakajima, Shingo AU - Nakajima S AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Faculty of Health Science, Hokkaido University, Sapporo, Japan. FAU - Numakawa, Tadahiro AU - Numakawa T AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. Electronic address: numakawa.yyrmk@gmail.com. FAU - Adachi, Naoki AU - Adachi N AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Biomedical Chemistry, Kwansei Gakuin University, Sanda, Japan. FAU - Ooshima, Yoshiko AU - Ooshima Y AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Molecular Pharmacology, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. FAU - Odaka, Haruki AU - Odaka H AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan. FAU - Yoshimura, Aya AU - Yoshimura A AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. FAU - Kunugi, Hiroshi AU - Kunugi H AD - Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151024 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*biosynthesis/*genetics MH - Cells, Cultured MH - Cerebral Cortex/cytology/*metabolism MH - Cyclic AMP Response Element-Binding Protein/biosynthesis/genetics MH - Neurons/*metabolism MH - Protein Kinase Inhibitors/pharmacology MH - RNA, Messenger/biosynthesis/genetics MH - Rats MH - Rats, Wistar MH - Receptor, trkB/pharmacology MH - Signal Transduction/drug effects MH - Synapses/drug effects/metabolism/*physiology OTO - NOTNLM OT - BDNF OT - CREB OT - ERK OT - TrkB EDAT- 2015/11/26 06:00 MHDA- 2016/09/16 06:00 CRDT- 2015/11/25 06:00 PHST- 2015/02/04 00:00 [received] PHST- 2015/10/08 00:00 [revised] PHST- 2015/10/20 00:00 [accepted] PHST- 2015/11/25 06:00 [entrez] PHST- 2015/11/26 06:00 [pubmed] PHST- 2016/09/16 06:00 [medline] AID - S0197-0186(15)30059-0 [pii] AID - 10.1016/j.neuint.2015.10.009 [doi] PST - ppublish SO - Neurochem Int. 2015 Dec;91:55-61. doi: 10.1016/j.neuint.2015.10.009. Epub 2015 Oct 24.