Folate metabolism regulates oligodendrocyte survival and differentiation by modulating AMPKα activity

Qinjie Weng, Jiajia Wang, Jiaying Wang, Biqin Tan, Jing Wang, Haibo Wang, Tao Zheng, Q. Richard Lu, Bo Yang, Qiaojun He

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 AMPKα to promote oligodendrocyte survival and differentiation. Moreover, activation of AMPKα 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/AMPKα axis in regulating oligodendrocyte survival and myelination during CNS development.

Original languageEnglish (US)
Article number1705
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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AMP-Activated Protein Kinases
Oligodendroglia
Folic Acid
Tetrahydrofolate Dehydrogenase
Micronutrients
Methotrexate
Up-Regulation
Carbon
Maintenance
Pharmacology
DNA
Enzymes

ASJC Scopus subject areas

  • General

Cite this

Folate metabolism regulates oligodendrocyte survival and differentiation by modulating AMPKα activity. / Weng, Qinjie; Wang, Jiajia; Wang, Jiaying; Tan, Biqin; Wang, Jing; Wang, Haibo; Zheng, Tao; Lu, Q. Richard; Yang, Bo; He, Qiaojun.

In: Scientific Reports, Vol. 7, No. 1, 1705, 01.12.2017.

Research output: Contribution to journalArticle

Weng, Q, Wang, J, Wang, J, Tan, B, Wang, J, Wang, H, Zheng, T, Lu, QR, Yang, B & He, Q 2017, 'Folate metabolism regulates oligodendrocyte survival and differentiation by modulating AMPKα activity', Scientific Reports, vol. 7, no. 1, 1705. https://doi.org/10.1038/s41598-017-01732-1
Weng, Qinjie ; Wang, Jiajia ; Wang, Jiaying ; Tan, Biqin ; Wang, Jing ; Wang, Haibo ; Zheng, Tao ; Lu, Q. Richard ; Yang, Bo ; He, Qiaojun. / Folate metabolism regulates oligodendrocyte survival and differentiation by modulating AMPKα activity. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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AU - Wang, Jiajia

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AU - Tan, Biqin

AU - Wang, Jing

AU - Wang, Haibo

AU - Zheng, Tao

AU - Lu, Q. Richard

AU - Yang, Bo

AU - He, Qiaojun

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