Effects of nuclear receptors RXRγ and PPARγ activation in Neural progenitor cell and Oligodendroglial progenitor cell primary cultures.

RODRÍGUEZ, DEBORA; MATHIEU, PATRICIA A.; ADAMO A.M.

Buenos Aires

Congreso; XXXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; 2022

Sociedad Argentina de Investigación en Neurociencias.

CNS demyelination is a pathological process through which myelin is lost from around axons, while remyelination is the process of myelin formation by oligodendrocytes (OLs). Retinoid X receptors (RXRs) are nuclear receptors forming homodimers or heterodimers with peroxisome proliferator-activated receptors (PPARs), which regulate OL differentiation and maturation. The aim of the present work was to study the activation of RXRγ by specific ligand 9 cis retinoic acid (9 cis Ra) in neural progenitor cell (NPC) and oligodendroglial precursor cell (OPC) primary cultures and whether such activation is mediated by heterodimerization with PPARγ. NPCs obtained from the subventricular zone of young adult rats and OPCs obtained from the cerebral cortex of newborn rats were treated with 9 cis Ra or vehicle for 4 days and in the presence or absence of PPARγ antagonist T0070907. NPC cultures show that 10 µM 9 cis Ra promoted a decrease in the proportion of Ki67+/PDGFRα+ cells and an increase in the proportion of mature MBP+ OLs. Also, 9 cis Ra promoted NPC glial cell fate, expanding the proportion of Nestin-/GFAP+ cells. Moreover, 1, 5 and 10 µM 9 cis Ra promoted an increase in the morphological complexity of PDGFRα+ OPCs, while 5 µM 9 cis Ra boosted the morphological complexity of mature MBP+ OLs. These results suggest that RXRγ participate in OPC proliferation and differentiation and may be thus considered possible therapeutic targets in the treatment of demyelinating diseases.