title: A role for hemopexin in oligodendrocyte differentiation and myelin formation.
abstract: Myelin formation and maintenance are crucial for the proper function of the CNS and are orchestrated by a plethora of factors including growth factors, extracellular matrix components, metalloproteases and protease inhibitors. Hemopexin (Hx) is a plasma protein with high heme binding affinity, which is also locally produced in the CNS by ependymal cells, neurons and glial cells. We have recently reported that oligodendrocytes (OLs) are the type of cells in the brain that are most susceptible to lack of Hx, as the number of iron-overloaded OLs increases in Hx-null brain, leading to oxidative tissue damage. In the current study, we found that the expression of the Myelin Basic Protein along with the density of myelinated fibers in the basal ganglia and in the motor and somatosensory cortex of Hx-null mice were strongly reduced starting at 2 months and progressively decreased with age. Myelin abnormalities were confirmed by electron microscopy and, at the functional level, resulted in the inability of Hx-null mice to perform efficiently on the Rotarod. It is likely that the poor myelination in the brain of Hx-null mice was a consequence of defective maturation of OLs as we demonstrated that the number of mature OLs was significantly reduced in mutant mice whereas that of precursor cells was normal. Finally, in vitro experiments showed that Hx promotes OL differentiation. Thus, Hx may be considered a novel OL differentiation factor and the modulation of its expression in CNS may be an important factor in the pathogenesis of human neurodegenerative disorders.
authors.affiliation: Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors.forename: Noemi
authors.initials: N
authors.lastname: Morello
authors.forename: Federico Tommaso
authors.initials: FT
authors.lastname: Bianchi
authors.forename: Paola
authors.initials: P
authors.lastname: Marmiroli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tonoli
authors.forename: Virginia
authors.initials: V
authors.lastname: Rodriguez Menendez
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D006466:Hemopexin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013234:Stem Cells / Q000378:metabolism
chemical_list: D006466:Hemopexin