The Role of Galectin-3: From Oligodendroglial Differentiation and Myelination to Demyelination and Remyelination Processes in a Cuprizone-Induced Demyelination Model

• DOI: 10.1007/978-3-319-40764-7_15
• Publication Date: 2016-10-06T02:35:53Z
• Authors: H. C. Hoyos; Mariel Marder; R. Ulrich; V. Gudi; M. Stangel; G. A. Rabinovich; L. A. Pasquini; J. M. Pasquini
• Keywords: Male; Galectin 3; REMYELINATION; MICROGLIA; Cuprizone; Mice; Phagocytosis; https://purl.org/becyt/ford/1.6; https://purl.org/becyt/ford/3.1; Glial Fibrillary Acidic Protein; Animals; https://purl.org/becyt/ford/3; Receptors, Immunologic; https://purl.org/becyt/ford/1; GALECTIN-3; Mice, Knockout; Brain; Cell Differentiation; Myelin Basic Protein; OLIGODENDROCYTES; Axons; Oligodendroglia; Gene Expression Regulation; Astrocytes; Leukocyte Common Antigens; Matrix Metalloproteinase 3; MMPs; Microglia; Demyelinating Diseases

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(Lgals3 -/-) and wild type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination.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.