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
刊名NEUROSCIENCE
2015
卷号284页码:234—246
关键词RAT SUBSTANTIA-NIGRA INDUCED NEUROTOXICITY DOPAMINERGIC-NEURONS CELL-DEATH NEURODEGENERATIVE DISORDERS MITOCHONDRIAL FERRITIN IN-VIVO CERULOPLASMIN DEFICIENCY EXPRESSION
英文摘要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.
收录类别SCI
语种英语
公开日期2015-12-24
内容类型期刊论文
源URL[http://ir.sinap.ac.cn/handle/331007/24404]  
专题上海应用物理研究所_中科院上海应用物理研究所2011-2017年
推荐引用方式
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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