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.
Curr Neurovasc Res
; 6(1): 42-53, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19355925
ABSTRACT
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 (p75(NTR)) 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator Neurotrófico Derivado do Encéfalo
/
Receptor trkB
/
Proliferação de Células
/
Células-Tronco Embrionárias
/
Neurônios
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Curr Neurovasc Res
Assunto da revista:
ANGIOLOGIA
/
NEUROLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Singapura