Galectin-3 protects the CNS in a model of Cuprizone- induced demyelination

HOYOS HC, PASQUINI LA, MARDER M AND PASQUINI JM

Congreso; 43nd Annual ASN Meeting; 2012

Multiple sclerosis (MS), the most common inflammatory demyelinating CNS disease affecting approximately one million adults, shares the basic pathological hallmark of CNS inflammatory demyelination (Wei Hu & Claudia F. Lucchinetti). MS also produces a significant oligodendrocyte (OLGs) disesase. There are few known therapies against demyelinating diseases. Previously, we found Galectin-3 promotes myelination in CNS by inducing OLG maturation. Here, we hipothesize that Galectin-3 protects CNS from the induced demyelination. Cuprizone (CPZ) induces a reproducible demyelination in the mice brain. The CPZ-induced demyelination is characterized by the OLGs loss, myelin sheats degeneration and astrocytes and microglia recruitment to the lesioned area. Lgals3-/- mice were fed from their 8th week of age with a diet CPZ 0.2% w/w during 6 weeks. At the 6th week of treatment mice were allowed to remyelinate, removing the CPZ diet. We have recently demonstrated CPZ induced-demyelination triggers an exacerbated astrocytic response as well as a microglial infiltration in Lgals3-/- mice vs. WT littermates. Electron microscopy showed a significant lack of myelinated axons in Lgals3-/- mice. Even though, the few myelinated axons, were nearly 50% less myelinated than controls. Behavioral assays demonstrated lower locomotory activity and innate anxiety levels in Lgals3-/- in comparison with their controls. Our results, allow us to say that Galectin-3 protects the CNS against the CPZ induced-demyelination, strongly supported by the enhanced severity of the injury observed in the myelin of Lgals3-/- treated with CPZ relative to WT mice. So, Galectin-3 could be suggested, in a future, as a terapeutic method for MS.