Galectin-1 circumvents lysolecithin-induced demyelination through the modulation of microglial polarization/phagocytosis and oligodendroglial differentiation.
Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins, binds to the common disaccharide [Galβ(1-4)-GlcNAc] on both N- and O-glycans decorating cell surface glycoconjugates. Current evidence supports a role for Gal-1 in the pathophysiology of multiple sclerosis (MS), one of the most prevalent chronic inflammatory diseases. Previous studies showed that Gal-1 exerts neuroprotective effects by promoting microglial deactivation in a model of autoimmune neuroinflammation and induces axonal regeneration in spinal cord injury. Seeking a model that could link demyelination, oligodendrocyte (OLG) responses and microglial activation, here we used a lysolecithin (LPC)-induced demyelination model to evaluate the ability of Gal-1 to preserve myelin without taking part in T-cell modulation. Gal-1 treatment after LPC-induced demyelination promoted a significant decrease in the demyelinated area and fostered more efficient remyelination, concomitantly with an attenuated oligodendroglial progenitor response reflecting less severe myelination damage. These results were accompanied by a decrease in the area of microglial activation with a shift toward an M2-polarized microglial phenotype and diminished astroglial activation. In vitro studies further showed that, mechanistically, Gal-1 targets activated microglia, promoting an increase in their myelin phagocytic capacity and their shift toward an M2 phenotype, and leads to oligodendroglial differentiation. Therefore, this study supports the use of Gal-1 as a potential treatment for demyelinating diseases such as MS.
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina.
Mariana
M
Rinaldi
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina.
Laura
L
Thomas
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina.
Patricia
P
Mathieu
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina.
Pablo
P
Carabias
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina.
Maria F
MF
Troncoso
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina.
Juana M
JM
Pasquini
Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME; CONICET), C1428 Buenos Aires, Argentina; Department of Biological Chemistry, School of Exact and Natural Sciences, University of Buenos Aires, C1428, Buenos Aires, Argentina.
Gabriel A
GA
Rabinovich
Department of Biological Chemistry, Institute of Chemistry and Biological Physicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University of Buenos Aires and National Research Council (CONICET), Argentina. Electronic address: laupasq@yahoo.com.
Laura A
LA
Pasquini
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure; D002454:Cell Differentiation / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D037483:Galectin 1 / Q000494:pharmacology* / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects*; D046509:Tissue Culture Techniques
D037483:Galectin 1; D008244:Lysophosphatidylcholines; D009419:Nerve Tissue Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571338:Cnp protein, mouse
Demyelination-remyelination; Galectin-1; Lysolecithin; Microglia; Phagocytosis