7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents

7,8-Dihydroxyflavone (7,8-DHF) is thought to be a promising therapeutic agent for various neurodegenerative diseases. The major purpose of this study was to investigate the neuroprotective effects of 7,8-DHF on the rotenone-induced motor deficit of Parkinson’s disease. Nine-month-old rats were treat...

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Main Authors: Shuke Nie, Kai Ma, Mingkuan Sun, Matthew Lee, Yang Tan, Guiqin Chen, Zhentao Zhang, Zhaohui Zhang, Xuebing Cao
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Parkinson's Disease
Online Access:http://dx.doi.org/10.1155/2019/9193534
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author Shuke Nie
Kai Ma
Mingkuan Sun
Matthew Lee
Yang Tan
Guiqin Chen
Zhentao Zhang
Zhaohui Zhang
Xuebing Cao
author_facet Shuke Nie
Kai Ma
Mingkuan Sun
Matthew Lee
Yang Tan
Guiqin Chen
Zhentao Zhang
Zhaohui Zhang
Xuebing Cao
author_sort Shuke Nie
collection DOAJ
description 7,8-Dihydroxyflavone (7,8-DHF) is thought to be a promising therapeutic agent for various neurodegenerative diseases. The major purpose of this study was to investigate the neuroprotective effects of 7,8-DHF on the rotenone-induced motor deficit of Parkinson’s disease. Nine-month-old rats were treated with rotenone (2 mg/kg/day, i.h.) for 5 weeks to establish the animal model of Parkinson’s disease (PD), and 7,8-DHF (5 mg/kg, i.p.) was administrated daily throughout the whole period of rotenone injection. Five weeks later, an open field test was used to assess the motor ability of the animals. TH immunostaining was performed to evaluate rotenone-induced neurotoxicity on substantia nigra (SN) dopaminergic neurons and the DA terminals in the striatum. Western blot analyses were used to examine the expressions of TH, BDNF/TrkB signaling cascades, phospho-α-synuclein (Ser129), α-synuclein, and phospho-tau (Ser396) in SN. The results revealed that treatment with 7,8-DHF improved PD model’s behavioral performance and reduced dopaminergic neuron loss in the SN and striatum, associated with the activation of TrkB receptors and its signaling cascades, and reduced p-MAPK, p-α-synuclein, and p-tau. Collectively, these results indicated that 7,8-DHF displayed prominent neuroprotective properties, providing a promising therapeutic strategy for PD treatment.
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issn 2090-8083
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publishDate 2019-01-01
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series Parkinson's Disease
spelling doaj-art-ee5c4a4c01294ded8c42637241a797572025-02-03T01:09:49ZengWileyParkinson's Disease2090-80832042-00802019-01-01201910.1155/2019/919353491935347,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in RodentsShuke Nie0Kai Ma1Mingkuan Sun2Matthew Lee3Yang Tan4Guiqin Chen5Zhentao Zhang6Zhaohui Zhang7Xuebing Cao8Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAWhiting School of Engineering, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China7,8-Dihydroxyflavone (7,8-DHF) is thought to be a promising therapeutic agent for various neurodegenerative diseases. The major purpose of this study was to investigate the neuroprotective effects of 7,8-DHF on the rotenone-induced motor deficit of Parkinson’s disease. Nine-month-old rats were treated with rotenone (2 mg/kg/day, i.h.) for 5 weeks to establish the animal model of Parkinson’s disease (PD), and 7,8-DHF (5 mg/kg, i.p.) was administrated daily throughout the whole period of rotenone injection. Five weeks later, an open field test was used to assess the motor ability of the animals. TH immunostaining was performed to evaluate rotenone-induced neurotoxicity on substantia nigra (SN) dopaminergic neurons and the DA terminals in the striatum. Western blot analyses were used to examine the expressions of TH, BDNF/TrkB signaling cascades, phospho-α-synuclein (Ser129), α-synuclein, and phospho-tau (Ser396) in SN. The results revealed that treatment with 7,8-DHF improved PD model’s behavioral performance and reduced dopaminergic neuron loss in the SN and striatum, associated with the activation of TrkB receptors and its signaling cascades, and reduced p-MAPK, p-α-synuclein, and p-tau. Collectively, these results indicated that 7,8-DHF displayed prominent neuroprotective properties, providing a promising therapeutic strategy for PD treatment.http://dx.doi.org/10.1155/2019/9193534
spellingShingle Shuke Nie
Kai Ma
Mingkuan Sun
Matthew Lee
Yang Tan
Guiqin Chen
Zhentao Zhang
Zhaohui Zhang
Xuebing Cao
7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents
Parkinson's Disease
title 7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents
title_full 7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents
title_fullStr 7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents
title_full_unstemmed 7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents
title_short 7,8-Dihydroxyflavone Protects Nigrostriatal Dopaminergic Neurons from Rotenone-Induced Neurotoxicity in Rodents
title_sort 7 8 dihydroxyflavone protects nigrostriatal dopaminergic neurons from rotenone induced neurotoxicity in rodents
url http://dx.doi.org/10.1155/2019/9193534
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