Participation of nuclear receptors PPARγ and RXR in the remyelination process

LAURA IVONNE GOMEZ PINTO; PATRICIA MATHIEU; DEBORA VANESA RODRIGUEZ; ANA ADAMO

Cordoba

Congreso; XXXIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2018

Demyelination in the CNS is a pathological process resulting from a direct insult on oligodendrocytes (OL), while remyelination is the repair process by which oligodendroglial precursor cells (OPC) restore myelin sheaths to demyelinated axons. Recent work has proven a significant increase in the transcript of retinoid X receptor γ (RXRγ) during remyelination in mice. RXRs are nuclear receptors forming homodimers or heterodimers with peroxisome proliferator activator proteins (PPARs), which regulate OL differentiation and maturation. The aim of the present work is to study the joint activation of RXRγ and PPARγ by specific agonists 9 cis retinoic acid (RA) and pioglitazone (PIO), respectively, and their impact on remyelination through in vitro and in vivo experiments. NPC obtained from the SVZ were treated with RA, PIO, PIO+RA or their vehicle for 4 days. PIO treatment rendered a higher proportion of PDGFRα+/KI67+ cells. In contrast, RA cultures showed a higher proportion of MBP+ cells, with no significant differences in the PIO+RA condition regarding vehicle. For in vivo experiments, cuprizone (CPZ)-demyelinated mice were stereotaxically injected vehicle or PIO+RA, unilaterally into the corpus callosum (CC) and sacrificed 7 days after injection. Immunohistochemical and Western blot analyses of the CC rendered a decrease in the proportion of Iba-1+ and GFAP+ cells as a consequence of PIO+RA treatment, together with an increase in myelin deposition. These preliminary results hint at a pro-myelinating and anti-inflammatory effect of RXRγ and PPARγ activation, respectively.