Past Issue

Volume 12, Supplement 1,Winter 2011 (Presented at The 1st International Student Congress) Pages: 35-36

O-38: Effects of PPARγ Agonist and Antagonist Treatment on Mature Neural Differentiation


Objective: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor super- family of ligand-activated transcription factors and are comprised of three isoforms (α, β and γ) which are encoded by three distinct genes. The activation processes of PPARs are mediated through their ligands. Two main groups of ligands for PPARγ include fatty acids and thiazolidinediones (TZDs). PPARγ is widely expressed in the embryo mouse brain and in neuronal stem cells (NSC) from both embryo and adult mouse brains. Despite of extensive literature on the anti-inflammatory action of PPARγ in neural neurodegenerative disease, however, studies on the role of PPARγ in neural differentiation has been very limited. In the present study, we investigated effects of PPARγ agonist and antagonist on neural precursor formation and differentiation from mouse embryonic stem cells (mESCs). Materials and Methods: For formation of neural precursor cells, embryoid bodies were derived from mouse embryonic stem cells by 2days culture in hanging &lt;font&gt;<font>drop</font>&lt;/font&gt;s, 4 days in suspensions in presence of retinoic acid. For differentiation and formation of mature neural cells, the embryo bodies were plated in neurobasal medium and assessed 7 days post culture in neurobasal medium. For evaluation of the role of PPARγ on neural differentiation of neural precursor cells, agonist (Rosiglitazone) and antagonist (GW9662) of PPARγ were added during 7days of post plating in neurobasal medium and was investigated expression of neural markers by Real-time PCR. These results were confirmed by staining. Results: To investigate the role of PPARγ on neural differentiation of neural precursor cells EBs were treated with RA and plated in neurobasal medium include PPARγ agonist and antagonist. The expression of MapII and β-tubulinIII (mature neuron markers) and GFAP (mature glial marker) were evaluated on day 14. Assessment of mature neuron and glial markers were not affected by PPARγ agonist. Moreover the results revealed that GW9662, PPARγ antagonist, did not significant effect on expression of neuron markers (MapII and β-tubulinIII), while inactivation of PPARγ decreased the expression of glial marker (GFAP). These observations were further confirmed by staining of β-tubulinIII. Conclusion: This result suggests that PPARγ influence on glial cells formation.These results demonstrated PPARγ maybe has a critical role in neural differentiation of neural precursor cells