Miglio Gianluca, Rattazzi Lorenza, Rosa Arianna C, Fantozzi Roberto
Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Via Pietro Giuria 9, 10125 Turin, Italy.
Neurosci Lett. 2009 Apr 24;454(2):134-8. doi: 10.1016/j.neulet.2009.03.014. Epub 2009 Mar 11.
Several evidences indicate that PPARgamma stimulation promotes neuronal differentiation. However, to date, no data describe the effects of PPARgamma agonists on neurite outgrowth. Here we have evaluated the effects of pioglitazone, a synthetic PPARgamma agonist, on differentiation and neurite outgrowth in SH-SY5Y human neuroblastoma cells. Our results show that pioglitazone promotes cell differentiation and the outgrowth of cell processes in a concentration-dependent manner with the maximal effect at 100 nM-1 microM. It significantly increases both the mean process length and the percentage of neurite-bearing cells. In addition, these effects are accompanied by significant activation of p42 and p44 mitogen-activated protein kinases. In conclusion, albeit preliminary, these findings suggest the possibility that PPARgamma stimulation may contribute to the development and maintenance of a proper neuronal connectivity within neuronal networks.
多项证据表明,过氧化物酶体增殖物激活受体γ(PPARγ)的激活可促进神经元分化。然而,迄今为止,尚无数据描述PPARγ激动剂对神经突生长的影响。在此,我们评估了合成的PPARγ激动剂吡格列酮对SH-SY5Y人神经母细胞瘤细胞分化和神经突生长的影响。我们的结果表明,吡格列酮以浓度依赖的方式促进细胞分化和细胞突起生长,在100 nM - 1 μM时效果最佳。它显著增加了平均突起长度和有神经突细胞的百分比。此外,这些作用伴随着p42和p44丝裂原活化蛋白激酶的显著激活。总之,尽管这些发现尚属初步,但它们提示了PPARγ激活可能有助于神经元网络内正常神经元连接的发育和维持的可能性。