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BRAIN IRON ACCUMULATION EXACERBATES THE PATHOGENESIS OF MPTP-INDUCED PARKINSON'S DISEASE | |
You, LH; Li, F; Wang, L; Zhao, SE; Wang, SM; Zhang, LL; Zhang, LH; Duan, XL; Yu, P; Chang, YZ | |
2015 | |
Source Publication | NEUROSCIENCE
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Volume | 284Pages:234—246 |
Subtype | 期刊文献 |
Abstract | Brain iron levels are significantly increased in Parkinson's disease (PD) and iron deposition is observed in the substantia nigra (SN) of PD patients. It is unclear whether iron overload is an initial cause of dopaminergic neuronal death or merely a byproduct that occurs in the SN of PD patients. In this study, ceruloplasmin knockout (CP-/-) mice and mice receiving an intracerebroventricular injection of ferric ammonium citrate (FAC) were selected as mouse models with high levels of brain iron. These mice were administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by intraperitoneal injection. Their behavior and the dopaminergic neuron damage to their substantia nigra pars compacta (SNpc) were assessed. These findings suggest that the injection of FAC or the absence of the CP gene may exacerbate both the observed apoptosis of TH-positive neurons and the behavioral symptoms of the MPTP-treated mice. The intracerebroventricular injection of deferoxamine (DFO) significantly alleviated the neuronal damage caused by MPTP in CP-/- mice. Furthermore, our findings suggest that the increased nigral iron content exacerbates the oxidative stress levels, promoting apoptosis through the Bcl-2/Bax pathway and the activated caspase-3 pathway in the brain. Therefore, iron overload in the brain exacerbates dopaminergic neuronal death in SNpc and leads to the onset of PD. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved. |
Keyword | Rat Substantia-nigra Induced Neurotoxicity Dopaminergic-neurons Cell-death Neurodegenerative Disorders Mitochondrial Ferritin In-vivo Ceruloplasmin Deficiency Expression |
Indexed By | SCI |
Language | 英语 |
Document Type | 期刊论文 |
Identifier | http://ir.sinap.ac.cn/handle/331007/24404 |
Collection | 中科院上海应用物理研究所2011-2020年 |
Recommended Citation GB/T 7714 | You, LH,Li, F,Wang, L,et al. BRAIN IRON ACCUMULATION EXACERBATES THE PATHOGENESIS OF MPTP-INDUCED PARKINSON'S DISEASE[J]. NEUROSCIENCE,2015,284:234—246. |
APA | You, LH.,Li, F.,Wang, L.,Zhao, SE.,Wang, SM.,...&Chang, YZ.(2015).BRAIN IRON ACCUMULATION EXACERBATES THE PATHOGENESIS OF MPTP-INDUCED PARKINSON'S DISEASE.NEUROSCIENCE,284,234—246. |
MLA | You, LH,et al."BRAIN IRON ACCUMULATION EXACERBATES THE PATHOGENESIS OF MPTP-INDUCED PARKINSON'S DISEASE".NEUROSCIENCE 284(2015):234—246. |
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