Cellular and Molecular Neurobiology
Author: Debora Vanesa Rodriguez | email: rodriguez-debora@hotmail.com
Débora Rodríguez 1°, Patricia Mathieu 2°, Ana M. Adamo 3°
1° Débora Rodríguez
2° Patricia Mathieu
3° Ana M. Adamo
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 RXR? 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 PPAR?. 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 PPAR? antagonist T0070907. NPC cultures show that 10 µM 9 cis Ra promoted a decrease in the proportion of Ki67+/PDGFR?+ 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 PDGFR?+ OPCs, while 5 µM 9 cis Ra boosted the morphological complexity of mature MBP+ OLs. These results suggest that RXR? participates in OPC proliferation and differentiation and may be thus considered possible therapeutic targets in the treatment of demyelinating diseases.