Effects of nuclear receptorPPARγ and RXR activation on NPC and OPC primary cultures

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

Buenos Aires

Congreso; XXXV SAN Annual Meeting; 2020

Sociedad Argentina de Investigación en Neurociencias

CNS demyelination is a pathological process by which myelin is lost from around axons, while remyelination is the repair process by which oligodendrocytes (OL) restore myelin to demyelinated axons. Retinoid X (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 primary cultures of neural progenitor cells (NPC)obtained from the SVZ of young adult rats, and oligodendroglial precursor cells (OPC), microglia and astrocytesobtained from the cerebral cortex of newborn rats. Results show that 10 µM RA induced a significant increase in GFAP+astrocytes at the expense of Nestin+/GFAP+ cells derived from NPC,concomitantly with a significant decrease in the proportion of proliferative Ki67+ cells. Also, 10 µM RAincreased the morphological complexity of both PDGFRα+ OPC and MBP+ OL, an effect also observed after 3-day treatment with 1 and 5 µM PIO. Microglia treatment with 5 µM PIO increased the production of NO induced by LPS, and astrocyte treatment with 5 µM PIO and 10 µM RAshowed an increase in the number of GFAP+ cells. These results suggest the participation of RXRγ and PPARγ in OPC differentiationand the microglial and astrocyte response,whichmay be relevant to myelin repair.