IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A NEW ROLE OF GALECTIN-1 IN AXONAL REGENERATION IN SPINAL CORD INJURY
Autor/es:
HÉCTOR R QUINTÁ, LAURA A PASQUINI, GABRIEL F RABINOVICH, JUANA M PASQUINI.
Lugar:
Cancun
Reunión:
Congreso; ISN-ASN Cancun 2013 meeting; 2013
Resumen:
Galectins (Gals) are a family of soluble lectins that, when bind b-Galactosides, form multivalent complex with glycoconjugates of the cellular surface and induce a modulation of intracellular signaling pathways for differentiation and survival. Recently, it was described a relationship between the immunosuppressor role of Gal-1 and microglia in a neurodegenerative autoimmune pathology (cita). However, its action at the neuronal level is poorly understood. Neuropilin-1 (Nrp-1) is a neuronal receptor, which is target of Semaphorin 3A (Sema3A), the latter being an anti-attractant of axonal growth. In addition, it was described in non-neuronal systems that Nrp-1 is target of Gal-1. Our aim was to study the role of Gal-1 in traumatic spinal cord injury (TSCI), since Sema3A expression is “turn on” in TSCI and prevents the axonal regeneration via Nrp-1. Gal-1 knockout mice (Lgals1-/-) were used performing a full TSCI at the thoracic level (T9-T10). These mice were treated with different concentration of recombinant Gal-1. We demonstrated that mice Lgals1-/- treated with 5 µg of Gal-1 have a functional recovery of motricity 6 days post-treatment, structurally associated to neuronal repopulation and high axonal regeneration. In addition, we observed that microglial response was “turned off” only in mice Lgals1-/- treated with Gal-1 whereas in mice (Lgals1-/- and Wild Type -WT-) treated with vehicle or WT mice treated with 5 mg of Gal-1 this process did not occur and also in the last case there was astrocyte hypertrophy in the point of lesion. When Gal-1 was increased to 10 mg and applied in WT mice, the motor response and axonal regeneration was better than in those mice treated with 5 mg, whereby Gal-1 would have a pro-regenerative isoform-depending action (dimeric vs monomeric) which is directly linked to the concentration. In this last case, we found in the lesion a population of cells that co-expressed Nestin and BIII-Neuronal-Tubulin. Moreover, exogenous dimeric Gal-1 bounded injured motoneuron surface promoting a spread out of Nrp-1 since specific point (clustering) from cell surface, in this point using 3D confocal microscopy reconstruction we could see that Gal-1 and Nrp-1 are linked. Then, we determined by immunoprecipitation assay that only the dimeric form of Gal-1 interacted with Nrp-1. In addition, only the treatment with dimeric form of Gal-1 produced a functional motor recovery. In conclusion, the dimeric form of Gal-1 binds Nrp-1, (a protein-glycan interaction), and promotes the neuronal regeneration probably avoiding the binding between Sema3A and Nrp-1 receptor and blocking the inhibitory effect on neuronal regeneration.