Brain-derived neurotrophic factor stimulates proliferation and differentiation of neural stem cells, possibly by triggering the Wnt/ß-catenin signaling pathway.
J Neurosci Res
; 91(1): 30-41, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23023811
ABSTRACT
Brain-derived neurotrophic factor (BDNF) has critical functions in promoting survival, expansion, and differentiation of neural stem cells (NSCs), but its downstream regulation mechanism is still not fully understood. The role of BDNF in proliferation and differentiation of NSCs through Wnt/ß-catenin signaling was studied via cell culture of cortical NSCs, Western blotting, immunocytochemistry, and TOPgal (Wnt reporter) analysis in mice. First, BDNF stimulated NSC proliferation dose dependently in cultured neurospheres that exhibited BrdU incorporation and neuronal and glial differentiation abilities. Second, BDNF effectively enhanced cell commitment to neuronal and oligodendrocytic fates, as indicated by increased differentiation marker Tuj-1 (neuronal marker), CNPase (oligodendrocyte marker), and neuronal process extension. Third, BDNF upregulated expression of Wnt/ß-catenin signaling (Wnt1 and free ß-catenin) molecules. Moreover, these promoting effects were significantly inhibited by application of IWR1, a Wnt signaling-specific blocker in culture. The TOPgal mouse experiment further confirmed BDNF-triggered Wnt signaling activation by ß-gal labeling. Finally, an MEK inhibition experiment showed a mediating role of the microtubule-associated protein kinase pathway in BDNF-triggered Wnt/ß-catenin signaling cascades. This study overall has revealed that BDNF might contribute to proliferation and neuronal and oligodendrocytic differentiation of NSCs in vitro, most possibly by triggering the Wnt/ß-catenin signaling pathway. Nevertheless, determining the exact cross-talk points at which BDNF might stimulate Wnt/ß-catenin signaling pathway in NSC activity requires further investigation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Fator Neurotrófico Derivado do Encéfalo
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Proliferação de Células
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Células-Tronco Neurais
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Via de Sinalização Wnt
Limite:
Animals
Idioma:
En
Revista:
J Neurosci Res
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China