Evidence for the contribution of BDNF-TrkB signal strength in neurogenesis: An organotypic study

Abstract

The importance of neurotrophins, especially brain-derived neurotrophic factor (BDNF) in the regulation of mammalian neurogenesis has been extensively studied. However, the exact effects of BDNF on cell proliferation and neurogenesis remain controversial. Here we tried to use an organotypic hippocampal slice culture (OHSC) to precisely control the concentration of BDNF and investigate their effects on neuro- and gliogenesis in vitro. With chronic supplementation of various concentration of the recombinant BDNF in culture medium, the number of newly born neurons was highly increased in a concentration dependent manner, while the number of glial cells remained unchanged. Blocking TrkB-BDNF signal pathway led to inhibition of neurogenesis. Time series analysis of BDNF and TrkB expression revealed relative low levels of BDNF and TrkB expression during early culture period, which might account for the results that early BDNF supplementation was more effective in the promotion of neurogenesis than late supplementation. These observations suggested that appropriate development-related modulation of BDNF-TrkB signal strength might impact on the initiation and maintenance of neurogenesis.