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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 PublicationNEUROSCIENCE
Volume284Pages:234—246
Subtype期刊文献
AbstractBrain 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.
KeywordRat Substantia-nigra Induced Neurotoxicity Dopaminergic-neurons Cell-death Neurodegenerative Disorders Mitochondrial Ferritin In-vivo Ceruloplasmin Deficiency Expression
Indexed BySCI
Language英语
Document Type期刊论文
Identifierhttp://ir.sinap.ac.cn/handle/331007/24404
Collection中科院上海应用物理研究所2011-2019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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