title: The Role of Galectin-3: From Oligodendroglial Differentiation and Myelination to Demyelination and Remyelination Processes in a Cuprizone-Induced Demyelination Model.
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(Lgals3-/-) and wild type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination.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.
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, Institute of Chemistry and Biological Physical Chemistry (IQUIFIB), Buenos Aires, Argentina.|School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: H C
authors.initials: HC
authors.lastname: Hoyos
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, Institute of Chemistry and Biological Physical Chemistry (IQUIFIB), Buenos Aires, Argentina.|School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Buenos Aires, Argentina.
authors.forename: Mariel
authors.initials: M
authors.lastname: Marder
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Ulrich
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for System Neurosciences, Hannover, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Gudi
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.|Center for System Neurosciences, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stangel
authors.affiliation: Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME; CONICET), C1428, Buenos Aires, Argentina.|Laboratory of Functional Glycomics, Department of Biological Chemistry, Faculty of Exact and Natural Sciences, University of Buenos Aires, C1428, Buenos Aires, Argentina.
authors.forename: G A
authors.initials: GA
authors.lastname: Rabinovich
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, Institute of Chemistry and Biological Physical Chemistry (IQUIFIB), Buenos Aires, Argentina.|School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Buenos Aires, Argentina.|Dpto. de Qca Biol, FFyB-UBA, Junín 956, C1113, Bs as, Argentina.
authors.forename: L A
authors.initials: LA
authors.lastname: Pasquini
authors.affiliation: Department of Biological Chemistry, School of Pharmacy and Biochemistry, Institute of Chemistry and Biological Physical Chemistry (IQUIFIB), Buenos Aires, Argentina. jpasquin@qb.ffyb.uba.ar.|School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Buenos Aires, Argentina. jpasquin@qb.ffyb.uba.ar.|Dpto. de Qca Biol, FFyB-UBA, Junín 956, C1113, Bs as, Argentina. jpasquin@qb.ffyb.uba.ar.
authors.forename: J M
authors.initials: JM
authors.lastname: Pasquini
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000534:rehabilitation; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics*; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D037502:Galectin 3; D005904:Glial Fibrillary Acidic Protein; C485095:Lgals3 protein, mouse; D004676:Myelin Basic Protein; D011971:Receptors, Immunologic; C424125:TREM-2b receptor; D014409:Tumor Necrosis Factor-alpha; C528900:glial fibrillary astrocytic protein, mouse; D003471:Cuprizone; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D019278:Matrix Metalloproteinase 3
keywords: Cuprizone; Demyelination; Galectin-3; MMPs; Microglia; Myelination; Oligodendrocytes; Remyelination