The Divalent Metal Transporter 1 (DMT1) Is Required for Iron Uptake and Normal Development of Oligodendrocyte Progenitor Cells

CHELI V,GONZALEZ SANTIAGO DA,MARZIALI LN,ZAMORA NN, GUITART ME, SPREUER V, PASQUINI JM AND PAEZ PM MARZIALI LN, ZAMORA NN, GUITART ME, SPREUER V, PASQUINI JM AND PAEZ PM

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Año: 2018 vol. 38 p. 9142 - 9159

0270-6474

The divalent metal transporter 1 (DMT1) is a multimetal transporter with a primary role in iron transport. Although DMT1 has beendescribed previously in the CNS, nothing was known about the role of this metal transporter in oligodendrocyte maturation and myelination.To determine whether DMT1 is required for oligodendrocyte progenitor cell (OPC) maturation, we used siRNAs and the Cre-loxsystem to knock down/knock out DMT1 expression in vitro as well as in vivo. Blocking DMT1 synthesis in primary cultures of OPCsreduced oligodendrocyte iron uptake and significantly delayed OPC development. In vivo, a significant hypomyelination was found inDMT1conditional knock-out mice in whichDMT1was postnatally deleted in NG2- or Sox10-positive OPCs. The brain ofDMT1knock-outanimals presented a decrease in the expression levels of myelin proteins and a substantial reduction in the percentage of myelinatedaxons. This reduced postnatal myelination was accompanied by a decrease in the number of myelinating oligodendrocytes and a rise inproliferating OPCs. Furthermore, using the cuprizone model of demyelination, we established that DMT1 deletion in NG2-positive OPCslead to less efficient remyelination of the adult brain. These results indicate that DMT1 is vital for OPC maturation and for the normalmyelination of the mouse brain.