Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway

The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis...

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Main Authors: Wei Zhang, Hong He, Hujie Song, Junjie Zhao, Tao Li, Leitao Wu, Xiaojun Zhang, Jianzong Chen
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Parkinson's Disease
Online Access:http://dx.doi.org/10.1155/2016/9450137
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author Wei Zhang
Hong He
Hujie Song
Junjie Zhao
Tao Li
Leitao Wu
Xiaojun Zhang
Jianzong Chen
author_facet Wei Zhang
Hong He
Hujie Song
Junjie Zhao
Tao Li
Leitao Wu
Xiaojun Zhang
Jianzong Chen
author_sort Wei Zhang
collection DOAJ
description The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP-) induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD.
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spelling doaj-art-0f32fa2ccbae4d9bbdae4cd56f98fc852025-02-03T06:11:41ZengWileyParkinson's Disease2090-80832042-00802016-01-01201610.1155/2016/94501379450137Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β PathwayWei Zhang0Hong He1Hujie Song2Junjie Zhao3Tao Li4Leitao Wu5Xiaojun Zhang6Jianzong Chen7Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaResearch Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Encephalopathy, Xi’an Encephalopathy Hospital of Traditional Chinese Medicine, Xi’an 710032, ChinaResearch Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaResearch Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaResearch Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaDepartment of Physics, Fourth Military Medical University, Xi’an 710032, ChinaResearch Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, ChinaThe degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP-) induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD.http://dx.doi.org/10.1155/2016/9450137
spellingShingle Wei Zhang
Hong He
Hujie Song
Junjie Zhao
Tao Li
Leitao Wu
Xiaojun Zhang
Jianzong Chen
Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway
Parkinson's Disease
title Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway
title_full Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway
title_fullStr Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway
title_full_unstemmed Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway
title_short Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway
title_sort neuroprotective effects of salidroside in the mptp mouse model of parkinson s disease involvement of the pi3k akt gsk3β pathway
url http://dx.doi.org/10.1155/2016/9450137
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