Oligodeoxynucleotide IMT504: Role on the microglial cell activation and oligodendrocyte progenitor cell proliferation and differentiation.

ALEXIS SILVA SILVA; ANA M. ADAMO; DEBORA RODRIGUEZ; PATRICIA MATHIEU

Buenos Aires

Congreso; Sociedad Argentina de Neurociencia; 2022

Sociedad Argentina de Investigación en Neurociencias.

Demyelination is a pathological process characterized by myelin loss from around axons, while remyelination is the repair response through the restoration of myelin and the resolution of functional deficits. Multiple sclerosis is a high-incidence inflammatory demyelinating disease in which remyelination frequently fails. IMT504 (IMT) is a non-CpG oligodeoxynucleotide consisting of 24 nucleotides and characterized by 2 specific PyNTTTTGT sequences. Based on IMT immunomodulatory effects and regenerative properties, this work aims to study its role in microglial activation and OL precursor (OPC) proliferation and differentiation. Primary cultures of OPCs and microglia were prepared from cerebral cortical tissue of 1- to 2-d-old rats. Microglia were treated for 24 h with IMT for RNA extraction. qPCR analyses were carried out to evaluate microglial IL-1?, iNOS, Arg1 and TGF- transcript expression. OPCs were treated with or without IMT, cultured for 2, 4 and 6 d and fixed for immunocytochemical assays on PDGFR+ OPCs, mature MBP+ OLs and Ki67+ proliferating cells.IMT produced an abrupt change in cell morphology compatible with microglial activation and an increase in IL-1 and iNOS transcript levels. IMT also reduced the percentage of OPCs after 4 d and increased the percentage of mature OLs after 4 and 6 d. These findings unveil potentially beneficial properties of IMT in neuroinflammation and oligodendrogenesis which may aid therapy development for demyelinating diseases.