Self-amplified BDNF transcription is a regulatory system for synaptic maturation in cultured cortical neurons. (December 2015)

• Record Type: Journal Article
• Authors: Nakajima, Shingo; Numakawa, Tadahiro; Adachi, Naoki; Ooshima, Yoshiko; Odaka, Haruki; Yoshimura, Aya; Kunugi, Hiroshi
• Is Part Of: Neurochemistry international. Volume 91(2015)
• Page Start: 55
• Page End: 61
• Publication Date: 2015-12
• Subjects: BDNF -- ERK -- CREB -- TrkB; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2015.10.009
• Languages: English
• ISSNs: 0197-0186

Abstract

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. Highlights: BDNF induced Bdnf mRNA expression in cultured cortical neurons. Involvement of MAPK and PI3K/Akt signaling in the self-amplification of BDNF. CREB and CaMK II were involved in the BDNF-induced Bdnf mRNA production. Newly-synthesized BDNF would contribute to post synaptic protein expression.