The peroxisome proliferator activated receptors (PPARs) are ligand-dependent transcription factors, classified as one of the members of nuclear hormone receptors super family. PPARs consist three major isoforms termed a, b/? and g which are encoded by distinct single-copy genes. PPARg comprises two variant forms g1 and g2, derived by an alternative splicing processing in related mRNA. The activation processes of PPARs are mediated through their ligands. Two main groups of ligands for PPARg include of fatty acids and Thiazolidinediones (TZDs). Among the fatty acids, deoxy D12, 14-prostaglandin J2 (15d-PGJ2) is considered as a natural ligand for PPARg. Moreover, TZDs, including Rosiglitazone and Ciglitazone, are the most widely studied PPARg ligands with anti-diabetic activity.
Mouse embryonic stem (mESCs) cells are pluripotent cells, are derived from the inner cell mass of the blastocyst and contain a capacity to differentiate into different cell linages in vitro. These properties have made mESCs cells as an attractive model to study of gene function during differentiation in vitro, especially for generation of neurons to treat the neurodegenerative disorders which are one of major cause of human disability.
In the present study, we have indicated that expression of PPAR g1 was increased upon retinoic acid treatment during neural precursor formation (EBd6 RA+) while, decreased upon plating or terminal neural differentiation stage. Therefore, the significant increase of PPARg1 expression upon RA treatment representing that PPARg1 might be involved in formation of neural precursor cells. These results demonstrated increment of PPARg expression in neurogenesis is due to RA treatment thus PPARg maybe has a critical role in neural differentiation of mESCs during neural precursor cell formation. In terminal neural differentiation, inactivation of PPAR by antagonist decreased the expression of mature glial marker (GFAP) while, did not influence the expression of mature neuronal markers (MapII, ?-tubulinIII). Therefore, PPARg influenced neuron differentiation of mESCs at early stage when neuron precursor cells were formed while, glial differentiation was influenced by PPARg during the differentiation stage.