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Folic Acid Acts Through DNA Methyltransferases to Induce the Differentiation of Neural Stem Cells into Neurons

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Abstract

The present study investigated the roles of folic acid and DNA methyltransferases (DNMTs) in the differentiation of neural stem cells (NSCs). Neonatal rat NSCs were grown in suspended neurosphere cultures and identified by their expression of SOX2 protein and capacity for self-renewal. Then NSCs were assigned to five treatment groups for cell differentiation: control (folic acid-free differentiation medium), low folic acid (8 μg/mL), high folic acid (32 μg/mL), low folic acid and DNMT inhibitor zebularine (8 μg/mL folic acid and 150 nmol/mL zebularine), and high folic acid and zebularine (32 μg/mL folic acid and 150 nmol/mL zebularine). After 6 days of cell differentiation, immunocytochemistry and western blot analyses were performed to identify neurons by β-tubulin III protein expression and astrocytes by GFAP expression. We observed that folic acid increased DNMT activity which may be regulated by the cellular S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and the abundance of neurons but decreased the number of astrocytes. Zebularine blocked these effects of folic acid. In conclusion, folic acid acts through elevation of DNMT activity to increase neuronal differentiation and decrease astrocytic differentiation in NSCs.

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Acknowledgments

This research was supported by grants from the National Natural Science Foundation of China (No. 81072289, 81130053 and 30901192).

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Authors and Affiliations

  1. Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, 300070, China

    Suhui Luo, Xumei Zhang, Min Yu, Hai Yan, Huan Liu & Guowei Huang

  2. Department of Exercise and Nutrition Sciences, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, 14214-8028, USA

    John X. Wilson

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  1. Suhui Luo
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  2. Xumei Zhang
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  3. Min Yu
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  4. Hai Yan
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  5. Huan Liu
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  7. Guowei Huang
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Corresponding author

Correspondence to Guowei Huang.

Additional information

Suhui Luo and Xumei Zhang contributed equally to this study

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Luo, S., Zhang, X., Yu, M. et al. Folic Acid Acts Through DNA Methyltransferases to Induce the Differentiation of Neural Stem Cells into Neurons. Cell Biochem Biophys 66, 559–566 (2013). https://doi.org/10.1007/s12013-012-9503-6

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  • DOI: https://doi.org/10.1007/s12013-012-9503-6

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