Cellular and Molecular Neurobiology
Author: Alejandro Bozzano | Email: alejandrobozzano@gmail.com
Alejando Bozzano 1°, Ana Adamo 1°, Patricia Mathieu 1°
1° Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, IQUIFIB-CONICET, Argentina.
Many central nervous system (CNS) diseases, such as multiple sclerosis, occur in the context of demyelination, a pathological process in which the myelin sheaths that surround axons are lost. Remyelination is a complex process where oligodendroglial precursor cells (OPC) proliferate, migrate and mature into oligodendrocytes to restore the myelin sheath in the CNS. Adult neural progenitor cells (NPC) from the subventricular zone (SVZ) can differentiate into OPC and contribute to the remyelination process. IMT504 is a non-CpG oligodeoxynucleotide consisting of 24 nucleotides and characterized by 2 specific PyNTTTTGT sequences. IMT504 has shown immunomodulatory effects and regenerative properties. In this context, our goal is to study the effect of IMT504 on NPC from the SVZ in a rat cuprizone (CPZ) demyelination model. Demyelinated rats were intracranially injected with IMT504 in the lateral ventricle after CPZ withdrawal. Seven days later we analyzed the contribution of NPC to remyelination by analyzing the different cell populations in the SVZ and the surrounding corpus callosum (CC) through immunohistochemistry. Our results showed an increase in OPC (PDGFR?+) and microglial (Iba1+CD68+) cell populations in the SVZ and CC. Altogether, these results show a potentially beneficial impact of IMT504 on NPC cell fate decisions toward a remyelinating lineage and microglial activation.