title: Transferrin is an essential factor for myelination.
abstract: It has been established that oligodendrocytes, the myelin forming cells, participate in iron homeostasis through the synthesis and secretion of transferrin. Here we investigated whether a correlation exists between myelination, the commonly studied function of oligodendrocytes, and that of transferrin synthesis and secretion. We used a proteolipid protein mutant, the myelin deficient rat, whose condition is characterized by severe hypomyelination. We compared the ontogenic profile for transferrin gene expression in mutants 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 intraparenchymal injection administered to P5 rat pups enabled mutant oligodendrocytes to synthesize myelin basic protein and to myelinate axons, indicating 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 transferrin deficiency during the premyelinating stage.
authors.affiliation: Mental Retardation Research Center, Department of Neurobiology, Brain Research Institute, UCLA School of Medicine, Los Angeles, CA 90024-1759, USA.
authors.forename: A
authors.initials: A
authors.lastname: Espinosa de los Monteros
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: P
authors.initials: P
authors.lastname: Zhao
authors.forename: C J
authors.initials: CJ
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Nazarian
authors.forename: T
authors.initials: T
authors.lastname: Pan
authors.forename: S
authors.initials: S
authors.lastname: Scully
authors.forename: R
authors.initials: R
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: de Vellis
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D004676:Myelin Basic Protein / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D014168:Transferrin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*