IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A chronic cuprizone-induced demyelination model for the development of therapies in the progressive stage of Multiple Sclerosis
Autor/es:
WIES MANCINI V.B.1, PASQUINI J.M.1, CORREALE J.D.2, PASQUINI L.A.1
Reunión:
Congreso; SAIC; 2016
Resumen:
A chroniccuprizone-induced demyelination model for the development of  therapies in the progressive stage ofMultiple SclerosisWies Mancini V.B.1, Pasquini J.M.1,Correale J.D.2, Pasquini L.A.11Department of Biological Chemistry,School of Pharmacy and Biochemistry, Institute of Chemistry and BiologicalPhysicochemistry (IQUIFIB), School of Pharmacy and Biochemistry, University ofBuenos Aires and National Research Council (CONICET), Argentina.2 Institute for Neurological research Dr. Raúl Carrea,FLENI Multiple Sclerosis(MS) is one of the most common causes of progressive disability affecting youngpeople in their productive life stage. Most patients initially present arelapsing-remitting course which, after 10 to 15-year evolution, becomesprogressive in up to 50% of untreated patients, with clinical symptoms slowlybut steadily deteriorating. In about 15% MS patients, however, diseaseprogression is relentless from disease onset. In recent decades, a betterunderstanding of relapsing-remitting MS disease mechanisms has led to thedevelopment of different disease-modifying therapies, reducing both severityand frequency of new relapses by modulating or suppressing the immune system.In contrast, therapeutic options available for progressive disease arecomparatively disappointing and remain a challenge. In this context, a 0.2%cuprizone (CPZ) diet administered to 5 to 6-week mice is known to inducedemyelination in the corpus callosum (acute model), while CPZ withdrawaltriggers a spontaneous remyelination process. When this diet is maintained for12 weeks (chronic model), remyelination usually fails, possibly due to neurodegeneration.The present work evaluates the use of the chronic model in the development oftherapies targeting the progressive stages of MS. Unlike features observed inthe acute model, our results in the chronic model show demyelination to reachthe spinal cord, as evidenced by immunohistochemical (MBP) and electronmicroscopy analyses of myelin. These findings were concomitant with astroglial(GFAP) and microglial (Griffonia and ED1) activation, as well as an increase inthe number of oligodendroglial progenitors (NG2). These findings hint at thepossible use of the chronic CPZ model to develop therapeutic agents enablingremyelination and preventing neurodegeneration.