Expression of peroxisome proliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neurons.

Neuronal differentiation is a complex process involving the sequential expression of several factors. The important role of lipid molecules in brain development is well known. Many fatty acid cell signaling activities are mediated by peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors belonging to the steroid, thyroid and retinoid nuclear receptor superfamily. They are activated by fatty acids and their derivatives. Different isotypes of PPARs (alpha, beta/delta and gamma) have distinct physiological functions depending on their different ligand activation profiles and tissue distribution. PPARs have been involved in neural cell differentiation and death as well as in inflammation and neurodegeneration. Although PPARs have been described in neurons by in situ studies, the presence and possible modulation of these receptors during neuronal differentiation has not been explored yet. In this study we analyzed the expression of PPARs and of their heterodimeric partners, RXRs, in embryonic rat cortical neurons during their in vitro maturation. Our results demonstrate the presence of PPARs alpha, beta/delta and gamma and of RXRs beta and gamma. PPARalpha, beta/delta and gamma are differentially modulated during culture time suggesting that they may be involved in neuronal maturation. In particular, we point toward the PPARbeta/delta isotype as a key factor in neuronal differentiation.