Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity

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. Dihydro...

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Autores principales:	Qinjie Weng, Jiajia Wang, Jiaying Wang, Biqin Tan, Jing Wang, Haibo Wang, Tao Zheng, Q. Richard Lu, Bo Yang, Qiaojun He
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e904908505214b8ba91ea44700ddaa7d
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spelling	oai:doaj.org-article:e904908505214b8ba91ea44700ddaa7d2021-12-02T11:51:11ZFolate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity10.1038/s41598-017-01732-12045-2322https://doaj.org/article/e904908505214b8ba91ea44700ddaa7d2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01732-1https://doaj.org/toc/2045-2322Abstract 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.Qinjie WengJiajia WangJiaying WangBiqin TanJing WangHaibo WangTao ZhengQ. Richard LuBo YangQiaojun HeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qinjie Weng Jiajia Wang Jiaying Wang Biqin Tan Jing Wang Haibo Wang Tao Zheng Q. Richard Lu Bo Yang Qiaojun He Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
description	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.
format	article
author	Qinjie Weng Jiajia Wang Jiaying Wang Biqin Tan Jing Wang Haibo Wang Tao Zheng Q. Richard Lu Bo Yang Qiaojun He
author_facet	Qinjie Weng Jiajia Wang Jiaying Wang Biqin Tan Jing Wang Haibo Wang Tao Zheng Q. Richard Lu Bo Yang Qiaojun He
author_sort	Qinjie Weng
title	Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
title_short	Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
title_full	Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
title_fullStr	Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
title_full_unstemmed	Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
title_sort	folate metabolism regulates oligodendrocyte survival and differentiation by modulating ampkα activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e904908505214b8ba91ea44700ddaa7d
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Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity

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