title: Ferritin binding in the developing mouse brain follows a pattern similar to myelination and is unaffected by the jimpy mutation.
abstract: We have previously provided evidence that ferritin binds selectively to white matter tracts in adult mouse and human brains. In cell culture experiments, ferritin binding is specifically localized to oligodendrocytes. The goal of the present study is to test the hypothesis that the developmental pattern for ferritin binding will coincide with the onset and progression of myelination. The first evidence of ferritin binding in the mouse brain is at 12 days of age and occurs within the brainstem. Ferritin binding persisted in the brainstem and expanded to the corpus callosum by 15-16 days of age. By 23-24 days of age ferritin binding had further extended to the striatal white matter. By adulthood, ferritin binding was strongly and selectively expressed throughout all white matter tracts. To begin to identify which factors may be involved in the induction of ferritin-binding proteins on oligodendrocytes, brains from the myelin mutant jimpy mice and unaffected littermates were examined at postnatal days 16-18. Jimpy mice were chosen because their oligodendrocytes fail to produce myelin or accumulate iron. Thus, using jimpy mice would elucidate whether these factors are necessary for ferritin-binding protein expression. Both the jimpy mutants and their controls exhibited saturable ferritin binding with similar binding densities and dissociation constants. Dissociation constants for ferritin binding in the unaffected littermates and jimpy mutant mice were 0.38 +/- 0.04 and 0.32 +/- 0.06 nM, respectively and binding densities were similar (1.1 +/- 0.09 and 0.96 +/- 0.12 fmol/mg, respectively). Our results demonstrate that expression of ferritin binding is dependent on the age of the oligodendrocytes and not dependent upon iron accumulation by oligodendrocytes or myelin production. We propose that iron delivery to oligodendrocytes is predominantly via ferritin and this method of iron uptake is unique to oligodendrocytes in the brain.
authors.affiliation: George M. Leader Laboratory for Alzheimer's Disease Research, Department of Neuroscience and Anatomy, M.S. Hershey Medical Center, Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Hulet
authors.forename: S
authors.initials: S
authors.lastname: Menzies
authors.forename: J R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D005293:Ferritins / Q000235:genetics / Q000493:pharmacokinetics*; D051379:Mice; D008816:Mice, Jimpy; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*
chemical_list: D005293:Ferritins