| First Author | Weng Q | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 1705 |
| PubMed ID | 28496133 | Mgi Jnum | J:310006 |
| Mgi Id | MGI:6759103 | Doi | 10.1038/s41598-017-01732-1 |
| Citation | Weng Q, et al. (2017) Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKalpha Activity. Sci Rep 7(1):1705 |
| abstractText | Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism for many cellular pathways including DNA synthesis, metabolism and maintenance. Folate deficiency has been associated with an increased risk of neurological disease, cancer and cognitive dysfunction. Dihydrofolate reductase (DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR activity in oligodendrocyte development has not been fully understood. Here we show that folate enhances oligodendrocyte maturation both in vitro and in vivo, which is accompanied with upregulation of oligodendrocyte-specific DHFR expression. On the other hand, pharmacological inhibition of DHFR by methotrexate (MTX) causes severe defects in oligodendrocyte survival and differentiation, which could be reversed by folate intake. We further demonstrate that folate activates a metabolic regulator AMPKalpha to promote oligodendrocyte survival and differentiation. Moreover, activation of AMPKalpha partially rescues oligodendrocyte defects caused by DHFR-inhibition both in vitro and in vivo. Taken together, these findings identify a previously uncharacterized role of folate/DHFR/AMPKalpha axis in regulating oligodendrocyte survival and myelination during CNS development. |
