Galectin-1 circumvents lysolecithin-induced demyelination through the modulation of microglial polarization/phagocytosis and oligodendroglial differentiation.

RINALDI M, THOMAS L, MATHIEU P, CARABIAS P, TRONCOSO MF, PASQUINI JM, RABINOVICH GA, PASQUINI LA.

NEUROBIOLOGY OF DISEASE

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2017 vol. 96 p. 127 - 143

0969-9961

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 supportsa role for Gal-1 in the pathophysiology of multiple sclerosis (MS), one of the most prevalent chronic inflammatorydiseases. Previous studies showed that Gal-1 exerts neuroprotective effects by promoting microglial deactivationin 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 myelinwithout taking part in T-cell modulation. Gal-1 treatment after LPC-induced demyelination promoted a significantdecrease in the demyelinated area and fostered more efficient remyelination, concomitantly with anattenuated oligodendroglial progenitor response reflecting less severe myelination damage. These results wereaccompanied by a decrease in the area of microglial activation with a shift toward an M2-polarized microglialphenotype and diminished astroglial activation. In vitro studies further showed that, mechanistically, Gal-1targets activated microglia, promoting an increase in their myelin phagocytic capacity and their shift towardan M2 phenotype, and leads to oligodendroglial differentiation. Therefore, this study supports the use of Gal-1as a potential treatment for demyelinating diseases such as MS.