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Adv Exp Med Biol ; 949: 311-332, 2016.
Article in English | MEDLINE | ID: mdl-27714696

ABSTRACT

The aim of this work was to combine our previously published results with our new data to show how galectin-3 (Gal-3) controls myelin integrity and function, promotes oligodendroglial cell differentiation, and regulates microglial responses to limit cuprizone- (CPZ)-induced demyelination and foster remyelination. In this study, 8-week-old Gal-3-deficient (Lgals3 -/-) and wild type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination. Our results show that remyelination was less efficient in Lgals3 -/- than in WT mice. Electron microscopic images from remyelinated sections in Lgals3 -/- mice revealed collapsed axons with a defective myelin wrap, while remyelinated WT mice had normal axons without relevant myelin wrap disruption. MMP-3 expression increased during remyelination in WT but not in Lgals3 -/- mice. The number of CD45+, TNFα+ and TREM-2b+ cells decreased only in WT mice only, with no alterations in Lgals3 -/- mice during demyelination and remyelination. Therefore, Gal-3 influences remyelination by mechanisms involving the tuning of microglial cells, modulation of MMP activity, and changes in myelin architecture.


Subject(s)
Astrocytes/pathology , Demyelinating Diseases/genetics , Galectin 3/genetics , Microglia/pathology , Oligodendroglia/pathology , Regeneration/genetics , Animals , Astrocytes/metabolism , Axons/metabolism , Axons/pathology , Brain/metabolism , Brain/pathology , Cell Differentiation , Cuprizone , Demyelinating Diseases/chemically induced , Demyelinating Diseases/pathology , Demyelinating Diseases/rehabilitation , Galectin 3/deficiency , Gene Expression Regulation , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Leukocyte Common Antigens/genetics , Leukocyte Common Antigens/metabolism , Male , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , Mice , Mice, Knockout , Microglia/metabolism , Myelin Basic Protein/genetics , Myelin Basic Protein/metabolism , Oligodendroglia/metabolism , Phagocytosis , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
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