Session: 9

PS9-12 | Demyelination/Remyelination in the CNS: role of ODN IMT504 in the repair process

Alexis Eduardo Silva Silva

Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica, Departamento de Química Biológica. IQUIFIB-CONICET.

Myelin is a highly specialized membrane which, in the CNS, is produced by oligodendrocytes (OLs). Demyelination is a pathological process characterized by myelin sheath loss from around axons, which results from genetic abnormalities, leukodystrophies, toxic demyelinating agents or inflammatory damage affecting both myelin and OLs. In turn, remyelination is the repairing response to demyelination and entails the restoration of myelin sheaths and the resolution of saltatory conduction and functional deficits. Multiple sclerosis is a high-incidence inflammatory demyelinating disease affecting young adults which involves demyelinated foci in different brain areas, sharp astrogliosis, microglial activation, persistent inflammation, and frequently unsuccessful remyelination. IMT504 is a non-CpG oligodeoxynucleotide consisting of 24 nucleotides (5`TCATCATTTTGTCATTTTGTCATT-3`) and characterized by 2 specific PyNTTTTGT sequences in its molecule, Py,being C or T and N being A, T, C or G. Based on IMT504 immunomodulatory effects and regenerative properties, this work aims to study the possible promyelinating effect of IMT504, either by acting on the polarization of microglia toward an M2 phenotype or by increasing the proliferation of OL precursors (OPCs) and their differentiation. To this end, IMT504 effects will be evaluated both in vitro, in primary cultures of neural stem cells (NSCs), OPCs and microglia, and in vivo, using the toxic cuprizone-induced demyelination model.