Ontogenetic oligodendrocyte maturation through gestational iron deprivation: The road not taken

MARÍA E. GUITART1 | MARIANELA VENCE1 | JORGE CORREALE2 | JUANA M. PASQUINI1 | MARÍA V. ROSATO-SIRI1

GLIA

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2020 vol. 67 p. 1760 - 1774

0894-1491

Developmental iron deficiency (dID) models facilitate the study of specific oligodendrocyte(OL) requirements for their progression to a mature state and subsequent contributionto myelination. In the current work, we used the dID model in transgenic miceexpressing green fluorescence protein under the CNPase promoter allowing the identificationof cells belonging to the oligodendroglial lineage, and the visualization of theentire myelin structure and single OL morphology. The present work evaluates dIDeffects on OL complexity in different brain areas. Control animals showed an increasein OL complexity both during development and along the anterior?posterior axis. Incontrast, dID animals exhibited an initial increase in CNPase+ cells with prevalence ofimmature-OL (i-OL), an effect later compensated during development by selectivedeath of those i-OL. As a consequence, developmental behavior was impaired in termsof body balance, muscle response, and sensorimotor functions. To explore why i-OL failto mature in dID, expression levels of transcriptional factors involved in the maturationof the OL lineage were studied. In nuclear fractions, dID animals showed an increase inHes5, which prevents the maturation of i-OL, and a decrease in Sox10, a positive regulatorof OL maturation. The cytoplasmic fractions showed a decrease in Olig1, which iscritical for precursor cell differentiation into premyelinating OL. Overall, the expressionlevels of Hes5, Sox10, and Olig1 in dID conditions correlated with an unfavorable OLmaturation profile. In sum, the current results provide further evidence of dID impacton myelination, keeping OL away from the maturational path.