Effects of nuclear receptors PPARγ and RXR activation in NPC and OPC primary cultures

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

Villa Carlos Paz

Congreso; XXXIV Reunion Anual Sociedad Argentina de Investigación en Neurociencias; 2019

Sociedad Argentina de Investigación en Neurociencias

CNS demyelination is a pathological process stemming from direct oligodendrocyte (OL) damage, while remyelination is the repair process by which oligodendroglial precursor cells (OPC) proliferate, migrate and mature into OL to restore myelin. RXRs are nuclear receptors forming homodimers, or else heterodimers with peroxisome proliferator-activated receptors (PPARs), which regulate OL differentiation and maturation. The aim of the present work is to study the single or joint activation of RXRγ and PPARγ by specific agonists 9 cis retinoic acid (RA) and pioglitazone (PIO), respectively, in neural progenitor cell (NPC) and OPC primary cultures. NPCs obtained from the SVZ of young adult rats and OPCs obtained from the cerebral cortex of newborn rats were treated with RA, PIO, PIO+RA or their vehicle for 4 days. In NPC cultures, results show that 5 µM PIO promoted an increase in the proportion of Nestin+/GFAP+ cells and the proliferation of NPC-derived PDGFRα+ cells. In contrast, 10 µM RA inhibited PDGFRα+ cell proliferation. However, combined treatment of 5 µM PIO + 10 µM RA exerted effects comparable to those of single PIO treatment. In turn, in OPC cultures, 10 µM RA treatment revealed a differentiating effect on PDGFRα+ cells and an increase in their morphological complexity. These results suggest the participation of RXRγ and PPARγ in OPC proliferation and differentiation and may be thus considered possible therapeutic targets in the treatment of demyelinating diseases.