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

Neurobiol Dis. 2016 Dec:96:127-143. doi: 10.1016/j.nbd.2016.09.003. Epub 2016 Sep 6.

Abstract

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.

Keywords: Demyelination-remyelination; Galectin-1; Lysolecithin; Microglia; Phagocytosis.

MeSH terms

  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / genetics
  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / metabolism
  • Animals
  • Animals, Newborn
  • Brain / drug effects
  • Brain / ultrastructure
  • Cell Differentiation / drug effects*
  • Cell Polarity / drug effects
  • Demyelinating Diseases* / chemically induced
  • Demyelinating Diseases* / drug therapy
  • Demyelinating Diseases* / pathology
  • Disease Models, Animal
  • Galectin 1 / pharmacology*
  • Galectin 1 / therapeutic use*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lysophosphatidylcholines / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / drug effects*
  • Microglia / ultrastructure
  • Nerve Tissue Proteins / metabolism
  • Oligodendroglia / drug effects*
  • Oligodendroglia / ultrastructure
  • Phagocytosis / drug effects*
  • Tissue Culture Techniques

Substances

  • Galectin 1
  • Lysophosphatidylcholines
  • Nerve Tissue Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
  • Cnp protein, mouse