Chronic mild stress accelerates the progression of Parkinson's disease in A53T alpha-synuclein transgenic mice
文献类型：期刊论文
| 作者 | Wu, Qimei; Yang, Xiaoyu; Zhang, Yu; Zhang, Lei; Feng, Linyin
|
| 刊名 | EXPERIMENTAL NEUROLOGY
 |
| 出版日期 | 2016-11 |
| 卷号 | 285页码:61-71 |
| ISSN号 | 0014-4886 |
| 关键词 | Chronic mild stress Parkinson's disease alpha-synuclein Dopamine Microglia |
| DOI | 10.1016/j.expneurol.2016.09.004 |
| 文献子类 | Article |
| 英文摘要 | Daily stress is associated with increased risk for various diseases, and numerous studies have provided evidence that environmental stress leads to deleterious effects on the central nervous system. However, it remains unclear whether chronic stress exacerbates the progression of Parkinson's disease (PD). To investigate this hypothesis, we determined the effect of chronic mild stress (CMS) on the pathogenesis of PD in a transgenic mice line that overexpresses the human A53T mutant alpha-synuclein (A53T Tg mice). We show that when exposed to CMS, male, but not female, A53TTg mice developed profound motor disabilities and exhibited olfactory sensitivity deficits. Pathological analysis also identified robust dopaminergic neuron degeneration and strong reduction of dopamine levels in A53T Tg male mice who underwent CMS treatment. Systematic examination of the abnormal aggregation of a-synuclein revealed a profound increase of inclusion in A53TTg male mice subject to CMS resembling key pathological changes of PD. An insight into the mechanism underlying stress leading to the acceleration of neurodegeneration in those with generic susceptibility, was revealed by evidence of microglia activation and elevated pro-inflammatory factor levels in A53T Tg male mice following CMS. Notably, these effects of CMS on the pathogenesis of PD showed a remarkable sexual dimorphism: only male A53T Tg mice exhibited exacerbation of the progression of PD. However, the molecular and cellular bases for this difference remains to be elucidated. Our results indicate a causative role for chronic mild stress using a PD animal model. Based on these findings, we propose that CMS acts as an environmental risk factor that leads to neuroinflammation and progressive neurodegeneration on a background of PD susceptibility. (C) 2016 Elsevier Inc. All rights reserved. |
| WOS关键词 | INDUCED NEUROTOXICITY ; DOPAMINERGIC-NEURONS ; CORTISOL RELEASE ; SEX-DIFFERENCES ; MOUSE MODEL ; BRAIN ; ONSET ; NEURODEGENERATION ; ACTIVATION ; MICROGLIA |
| 资助项目 | "Key New Drug Creation and Manufacturing Program" of the National Science & Technology Major Project[2014ZX09102-001-05] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA01040304] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| WOS记录号 | WOS:000386745700006 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275840]  |
| 专题 | 药理学第二研究室 |
| 通讯作者 | Feng, Linyin |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Chong Zhi Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Qimei,Yang, Xiaoyu,Zhang, Yu,et al. Chronic mild stress accelerates the progression of Parkinson's disease in A53T alpha-synuclein transgenic mice[J]. EXPERIMENTAL NEUROLOGY,2016,285:61-71. |
| APA | Wu, Qimei,Yang, Xiaoyu,Zhang, Yu,Zhang, Lei,&Feng, Linyin.(2016).Chronic mild stress accelerates the progression of Parkinson's disease in A53T alpha-synuclein transgenic mice.EXPERIMENTAL NEUROLOGY,285,61-71. |
| MLA | Wu, Qimei,et al."Chronic mild stress accelerates the progression of Parkinson's disease in A53T alpha-synuclein transgenic mice".EXPERIMENTAL NEUROLOGY 285(2016):61-71. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。