Oligodeoxynucleotide IMT504: Role on the oligodendrocyte progenitor cell proliferation, maduration and microglia cell proliferation, activation and phagocytic capacity

SILVA SILVA, ALEXIS; MATHIEU, PATRICIA A.; ADAMO A.M.

San Luis

Congreso; XXXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; 2023

Sociedad Argentina de Investigación en Neurociencias.

Demyelination consists in myelin loss from around axons, while remyelination restores myelin and resolves 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. Given the regenerative and immunomodulatory properties of IMT504, our work aims to study its role in microglial and oligodendrocyte (OL) progenitor cell (OPC) contribution to remyelination. Primary cultures of OPCs and microglia were obtained from cerebral cortical tissue of 1- to 2-day-old rats. OPCs were treated with or without IMT, cultured for 24h and fixed for immunocytochemistry (ICC) assays on proliferation. Also, OPCs were treated once or twice every 48h and fixed for ICC assays to evaluate PDGFRα+ OPCs and mature MBP+ OLs. Microglia were treated with or without IMT for 24h, subsequently incubated for 1h with fluorescent latex beads for phagocytosis assays, or cultured for 24h to assess proliferation. Results showed IMT-induced morphological changes compatible with microglia activation and an increase in their phagocytic capacity. IMT also reduced microglia proliferation. IMT also reduced OPC proliferation and induced an increase in their differentiation into mature OL. These findings support potentially beneficial properties of IMT which may aid therapy development for demyelinating diseases.