Recovery of locomotor activities in Spinal Cord Injury: A novel treatment to produce intra-axonal decrease of peroxide levels and reactivation of cytoskeleton dynamics in damaged axons

HR QUINTÁ

Mar del Plata, Argentina

Simposio; Sociedad Argentina de Investigación en Neruociencias; 2015

AbstractThe axonal growth cone collapse following spinal cord injury (SCI) is promoted by Semaphorin 3A (Sema3A) signalling via PlexinA4 surface receptor. This signalling triggers intracellular pathways that promote an increase of hydrogen peroxide levels and F-actin destabilization, inducing collapse and inhibition of axonal re-growth. Recently, we demonstrate for first time that Galectin-1 (Gal-1) an endogenous glycan-binding protein, in its dimeric form, promotes functional recovery of spinal lesions by interfering with inhibitory signals triggered by Semaphorin 3A (Sema3A) binding to Neuropilin-1/PlexinA4 complex (Quintá et. al. 2014). However, the intra-cellular mechanism of this process is totally unknown. Therefore, in this study, we successfully demonstrate that, only Galectin-1 (Gal-1) treatment, in its dimeric form but not in the monomeric form promotes the decrease of hydrogen peroxide levels and a re-polimerization of F-actin in the growth cone and in the filopodium of whole neurons. This treatment avoids the hydrogen peroxide production by Sema3A/plexinA4 signalling, and therefore avoids the growth cone collapse by F-actin depolimerization. To promote decrease of hydrogen peroxide levels, Gal-1 in its dimeric form needs in your structure an intact carbohydrate recognition domain. Furthermore, Gal-1 promotes an active endocytosis of PlexinA4 receptor, leaving the neuronal surface less sensitive to Sema3A effects. In summary, our results suggest that Gal-1 in its dimeric form promotes a re-activation of actin cytoskeleton dynamic by decreasing the peroxide levels via internalization of PlexinA4 receptor. This mechanism would explain not only the full axonal re-growth process but also, a "de novo" formation of synapses clustering, a axonal re-mielinization process and functional recovery of locomotor activities in an in-vivo SCI model (acute and chronic).