Self-amplified BDNF transcription is a regulatory system for synaptic maturation in cultured cortical neurons

Shingo Nakajima, Tadahiro Numakawa, Naoki Adachi, Yoshiko Ooshima, Haruki Odaka, Aya Yoshimura, Hiroshi Kunugi

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalNeurochemistry International
Volume91
DOIs
Publication statusPublished - 12-2015

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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