Ceruloplasmin deletion in myelinating glial cells induces myelin disruption and oxidative stress in the central and peripheral nervous systems
| Autor: | Veronica T. Cheli, Pablo M. Paez, G. Denaroso, Shaina L. Rosenblum, D.A. Santiago González |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Medicine (General)
QH301-705.5 Iron Clinical Biochemistry Ferroxidase activity medicine.disease_cause Biochemistry Neuroprotection Myelin Mice Myelination R5-920 medicine Animals Schwann cells Biology (General) Myelin Sheath biology Cell growth Oligodendrocytes Organic Chemistry Neurodegeneration Ceruloplasmin medicine.disease Cell biology Oligodendroglia Oxidative Stress medicine.anatomical_structure nervous system Apoptosis biology.protein Oxidative stress Research Paper |
| Zdroj: | Redox Biology Redox Biology, Vol 46, Iss, Pp 102118-(2021) |
| ISSN: | 2213-2317 |
| Popis: | Ceruloplasmin (Cp) is a ferroxidase enzyme that is essential for cell iron efflux and has been postulated to have a neuroprotective role. During the myelination process, oligodendrocytes (OLs) and Schwann cells (SCs) express high levels of Cp, but the role of this enzyme in glial cell development and function is completely unknown. To define the function of Cp in the myelination of the central and peripheral nervous systems, we have conditionally knocked-out Cp specifically in OLs and SCs during early postnatal development as well as in aged mice. Cp ablation in early OLs (postnatal day 2, P2) significantly affects the differentiation of these cells and the synthesis of myelin through the first four postnatal weeks. The total number of mature myelinating OLs was reduced, and the density of apoptotic OLs was increased. These changes were accompanied with reductions in the percentage of myelinated axons and increases in the g-ratio of myelinated fibers. Cp ablation in young myelinating OLs (P30 or P60) did not affect myelin synthesis and/or OL numbers, however, Cp loss in aged OLs (8 months) induced cell iron overload, apoptotic cell death, brain oxidative stress, neurodegeneration and myelin disruption. Furthermore, Cp deletion in SCs affected postnatal SC development and myelination and produced motor coordination deficits as well as oxidative stress in young and aged peripheral nerves. Together, our data indicate that Cp ferroxidase activity is essential for OLs and SCs maturation during early postnatal development and iron homeostasis in matured myelinating cells. Additionally, our results suggest that Cp expression in myelinating glial cells is crucial to prevent oxidative stress and neurodegeneration in the central and peripheral nervous systems. Graphical abstract Image 1 Highlights • Cp activity is essential for the development and function of myelinating glial cell. • Cp ablation delays oligodendrocyte and Schwann cell maturation. • Cp deletion interrupts the myelination of the central and peripheral nervous systems. • Cp deletion in aged oligodendrocytes induces cell dead and brain oxidative stress. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|