title: Folic acid acts through DNA methyltransferases to induce the differentiation of neural stem cells into neurons.
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.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Suhui
authors.initials: S
authors.lastname: Luo
authors.forename: Xumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Hai
authors.initials: H
authors.lastname: Yan
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.forename: John X
authors.initials: JX
authors.lastname: Wilson
authors.forename: Guowei
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D003562:Cytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D005492:Folic Acid / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D004248:DNA (Cytosine-5-)-Methyltransferases