Brain-Derived Neurotrophic Factor (BDNF) has Proliferative Effects on Neural Stem Cells through the Truncated TRK-B Receptor, MAP Kinase, AKT, and STAT-3 Signaling Pathways

Author(s): Omedul Islam, Tze X. Loo, Klaus Heese

Journal Name: Current Neurovascular Research

Volume 6 , Issue 1 , 2009

Become EABM
Become Reviewer


Neurospheres can be generated from the mouse fetal forebrain by exposing multipotent neural stem cells (NSCs) to epidermal growth factor (EGF). In the presence of EGF, NSCs can proliferate continuously while retaining the potential to differentiate into neurons, astrocytes and oligodendrocytes. We examined the expression pattern of the neurotrophin (NT) receptors tropomysin-related kinase (TRK)-A, TRK-B, TRK-C and p75 neurotrophin receptor (p75NTR) in NSCs and the corresponding lineage cells. Furthermore, we analyzed the action of the NT Brain-Derived Neurotrophic Factor (BDNF) on NSCs behavior. The effects of BDNF on NSC proliferation and differentiation were examined together with the signaling pathways by which BDNF receptors transduce signaling effects. We found that all the known NT receptors, including the truncated isoforms of TRK-B (t-TRK-B) and TRK-C (t-TRK-C), were expressed by Nestin-positive cells within the neurosphere. Proliferation was enhanced in Nestin-positive and BrdU-positive cells in the presence of BDNF. In particular, we show that t-TRK-B was abundantly expressed in NSCs and the corresponding differentiated glia cells while full length TRK-B (fl-TRK-B) was expressed in fully differentiated post-mitotic neurons such as the neuronal cells of the newborn mouse cortex, suggesting that BDNF may exert its proliferative effects on NSCs through the t-TRK-B receptor. Finally, we analyzed the cell fates of NSCs differentiated with BDNF in the absence of EGF and we demonstrate that BDNF stimulated the formation of differentiated cell types in different proportions through the MAP kinase, AKT and STAT-3 signaling pathways. Thus, the in-vivo regulation of neurogenesis may be mediated by the summation of signals from the BDNF receptors, in particular the t-TRK-B receptor, regulating physiological fates as diverse as normal neural replacement, excessive neural loss, or tumor development.

Keywords: Neural stem cells, neurotrophic factors, trk receptors

promotion: free to download

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2009
Page: [42 - 53]
Pages: 12
DOI: 10.2174/156720209787466028

Article Metrics

PDF: 119