a role for hemopexin in oligodendrocyte differentiation and myelin formation血液结合素的作用少突细胞分化和髓鞘的形成.pdfVIP

A Role for Hemopexin in Oligodendrocyte Differentiation and Myelin Formation 1 1 2 3 Noemi Morello , Federico Tommaso Bianchi , Paola Marmiroli , Elisabetta Tonoli , Virginia Rodriguez 2 1 2 3 1 Menendez , Lorenzo Silengo , Guido Cavaletti , Alessandro Vercelli , Fiorella Altruda , Emanuela Tolosano1* 1 Molecular Biotechnology Center, University of Turin, Turin, Italy, 2 Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy, 3 Neuroscience Institute of Turin, Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy 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