title: Self-amplified BDNF transcription is a regulatory system for synaptic maturation in cultured cortical neurons.
abstract: 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.
authors.affiliation: 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.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: 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.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.affiliation: 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.
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.affiliation: 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.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ooshima
authors.affiliation: 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.
authors.forename: Haruki
authors.initials: H
authors.lastname: Odaka
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D020813:Receptor, trkB
keywords: BDNF; CREB; ERK; TrkB