Neuroprotective Effect and Mechanism of Thiazolidinedione on Dopaminergic Neurons In Vivo and In Vitro in Parkinson's Disease

作者：Wang, Yanqin; Zhao, Weilin; Li, Ge; Chen, Jinhu; Guan, Xin; Chen, Xi; Guan, Zhenlong^*

来源：PPAR Research, 2017, 2017: 4089214.

DOI：10.1155/2017/4089214

• GAMMA AGONIST PIOGLITAZONE
• NEUROBLASTOMA SH-SY5Y CELLS
• NF-KAPPA-B
• PPAR-GAMMA
• MOUSE MODEL
• MITOCHONDRIAL DYSFUNCTION
• OXIDATIVE STRESS
• MPTP MODEL
• ROSIGLITAZONE
• NEURODEGENERATION

The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both in vitro and in vivo MPP+ /MPTP induced PD models. In vivo experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor-gamma coactivator of 1 alpha (PGC-1 alpha) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. From in vitro studies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1 alpha, nuclear respiratory factor 1 (NRF1), NRF2, and mitochondria fusion 2 (Mfn2), and inhibited mitochondria fission 1 (Fis1). We show that protein levels of Bcl-2 and ERK were reduced in the MPP+-treated group compared with the control group. This effect was observed to be reversed upon treatment with 2,4-thiazolidinedione, as Bcl-2 and ERK expression levels were increased. We also observed that levels of the apoptotic protein Bax showed opposite changes compared to Bcl-2 and ERK levels. The results from this study confirm that pioglitazone/2,4-thiazolidinedione is able to activate PGC-1 alpha and prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.

• 出版日期2017
• 单位河北省人民医院; 河北师范大学; 河北体育学院