Galectin-1 intranasal administration in the treatment of demyelinating diseases

57. SANTIAGO CASTERA, HERNAN AYAN, LAURA A PASQUINI

Buenos Aires

Congreso; GLIA Meeting; 2017

GLIA-Polo Científico y Tecnológico

Galectin-1 (Gal-1), a member of thehighly conserved family of animal lectins, participates in the pathophysiologyof Multiple Sclerosis (MS). Our recent studies show that Gal-1 exertsneuroprotective effects by promoting microglial deactivation and promotesaxonal regeneration by interfering with the inhibitory signals induced by thebinding of Sema3A to the NRP-1 / Plexin A4 complex. Moreover, our laboratory,using the lysolecithin-induced focal demyelination model, has demonstrated thatGal-1 produces a significant decrease in the demyelinated area, a moreefficient remyelination at the ultra-structural level, an attenuated responseof the oligodendroglial progenitors reflecting less myelin damage, as well as adecrease in the area of ​​microglial activation with a shift toward the M2 phenotypeand increased phagocytic capacity of myelin debris. As intracranial injection isnot practised for clinical purposes, it is essential to develop less invasivetechniques capable of delivering treatments to the central nervous system. Apromising way to send drugs to the brain is the intranasal route. Therefore,the aim proposed for the present project is to evaluate the route of Gal-1 intranasaladministration (iN) in the treatment of demyelinating diseases in a model of Cuprizone(CPZ)-induced demyelination. Our results show that Gal-1 is successfullydelivered to the rostral, middle and caudal areas of the brain, as it was detected24 h after iN by Western blot analysis in Gal-1 knockout mice.   Moreover, Gal-1 iN led to a decrease indemyelination and GFAP (astroglial marker) immunostaining in the corpuscallosum (CC), supporting Gal-1 iN use as a potential treatment for demyelinatingdiseases such as MS.