Transferrin is an essential factor for myelination

It has been established that oligodendrocytes, the myelin forming cells, pa rticipate in iron homeostasis through the synthesis and secretion of transf errin. Here we investigated whether a correlation exists between myelinatio n, the commonly studied function of oligodendrocytes, and that of transferr in synthesis and secretion. We used a proteolipid protein mutant, the myeli n deficient rat, whose condition is characterized by severe hypomyelination . We compared the ontogenic profile for transferrin gene expression in muta nts with that of unaffected rat pups through northern blot analysis and in situ hybridization. Surprisingly, transferrin synthesis was null in mutant oligodendrocytes. Next, we demonstrated that a single apo-transferrin intra parenchymal injection administered to P5 rat pups enabled mutant oligodendr ocytes to synthesize myelin basic protein and to myelinate axons, indicatin g that transferrin effects mutant oligodendrocyte maturation regardless of its source. Thus, transferrin availability is essential for oligodendrocyte maturation and function, and oligodendrocytes are most vulnerable to trans ferrin deficiency during the premyelinating stage.