title: Neuroprotective Effect and Mechanism of Thiazolidinedione on Dopaminergic NeuronsIn VivoandIn Vitroin Parkinson's Disease.
abstract: The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in bothin vitroandin vivoMPP+/MPTP induced PD models.In vivoexperimental 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-γcoactivator of 1α(PGC-1α) and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. Fromin vitrostudies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1α, 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-1αand prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.
authors.affiliation: Department of Physiology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Human Movement Science, Hebei Institute of Physical Education, Shijiazhuang, Hebei 050041, China.
authors.forename: Weilin
authors.identifier: 0000-0002-7431-7508
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Physiology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.
authors.forename: Jinhu
authors.identifier: 0000-0002-4923-5076
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Physiology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Physiology, College of Life Science, Hebei Normal University, Shijiazhuang, Hebei 050024, China.
authors.forename: Zhenlong
authors.identifier: 0000-0003-1930-6029
authors.initials: Z
authors.lastname: Guan