Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jan 1;8(1):578-85.
eCollection 2015.

Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells

Li Wang  1 , Yuan Liu  1 , Sen Li  1 , Zai-Yun Long  1 , Ya-Min Wu  1
Affiliations

Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells

Li Wang et al. Int J Clin Exp Pathol. .

Abstract

Neural stem cells (NSCs) are multipotent cells that have the capacity for differentiation into the major cell types of the nervous system, i.e. neurons, astrocytes and oligodendrocytes. Valproic acid (VPA) is a widely prescribed drug for seizures and bipolar disorder in clinic. Previously, a number of researches have been shown that VPA has differential effects on growth, proliferation and differentiation in many types of cells. However, whether VPA can induce NSCs from embryonic cerebral cortex differentiate into neurons and its possible molecular mechanism is also not clear. Wnt signaling is implicated in the control of cell growth and differentiation during CNS development in animal model, but its action at the cellular level has been poorly understood. In this experiment, we examined neuronal differentiation of NSCs induced by VPA culture media using vitro immunochemistry assay. The neuronal differentiation of NSCs was examined after treated with 0.75 mM VPA for three, seven and ten days. RT-PCR assay was employed to examine the level of Wnt-3α and β-catenin. The results indicated that there were more β-tublin III positive cells in NSCs treated with VPA medium compared to the control group. The expression of Wnt-3α and β-catenin in NSCs treated with VPA medium was significantly greater compared to that of control media. In conclusion, these findings indicated that VPA could induce neuronal differentiation of NSCs by activating Wnt signal pathway.

Keywords: Wnt-3α; differentiation; neural stem cells; valproic acid; β-catenin.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The growth and identification of NSCs in vitro. A. Representative photomicrograph of neurospheres in culture (bar = 75 µm). B. Representative photomicrograph of differentiated NSCs (bar = 160 µm). C. Immunocytochemical staining of purified NSCs with Nestin (bar = 80 µm). D. Immunocytochemical staining of NSCs with anti-Brd-U antibody (bar = 80 µm). E. Nucleus staining of NSCs with DAPI (bar = 75.55 µm). F. Immunocytochemical staining of differentiated neurons from neurospheres (green indicates neuron-specific label β-tubulin III, bar = 75.55 µm). G. Immunocytochemical staining of differentiated astrocytes from neurospheres(red indicates astrocyte-specific label GFAP, bar = 75.55 µm). H. Merge of F and G (bar = 75.55 µm).
Figure 2
Figure 2
Identification and quantification of differentiated neural cells cultured in VPA medium and control medium 7 days in vitro. A. Immunocytochemical staining of differentiated neural cells in different midium. β-tubulin III staining (green) indicates neurons; GFAP staining (red) indicates astrocytes. The nuclei were counterstained with DAPI (blue). (Scale bar = 75 µm). B. Quantification of differentiated neurons in two culture media. *P < 0.05 indicates statistical significance compared with control group.
Figure 3
Figure 3
RT-PCR analysis of Wnt-3α and β-catenin expression in NSCs cultured in VPA medium and control medium at 3, 7, 10 days in vitro. A. The expression of Wnt-3α in two groups. B. The expression of β-catenin in two groups. The level of Wnt-3α and β-catenin in VPA treated NSCs was higher than that in the control group. *P < 0.01 indicates statistical significance compared to the control group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Goh EL, Ma D, Ming GL, Song H. Adult neural stem cells and repair of the adult central nervous system. J Hematother Stem Cell Res. 2003;12:671–679. - PubMed
    1. Yin X, Li L, Zhang X, Yang Y, Chai Y, Han X, Feng Z. Development of neural stem cells at different sites of fetus brain of different gestational age. Int J Clin Exp Pathol. 2013;6:2757–2764. - PMC - PubMed
    1. Alvarez-Buylla A, Temple S. Stem cells in the developing and adult nervous system. J Neurobiol. 1998;36:105–110. - PubMed
    1. Gage FH. Mammalian neural stem cells. Science. 2000;287:1433–1438. - PubMed
    1. Ren H, Chen J, Wang Y, Zhang S, Zhang B. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis. Int J Clin Exp Pathol. 2013;6:230–341. - PMC - PubMed

Publication types

LinkOut - more resources