Increased vulnerability with aging to MPTP: the mechanisms underlying mitochondrial dynamics
Increased vulnerability with aging to MPTP: the mechanisms underlying mitochondrial dynamics
复制标题
随着衰老对 MPTP 的脆弱性增加：线粒体动力学的机制
DOI：
10.1179/1743132813y.0000000296
复制
发表时间：
2014-07
影响因子：
1.9
通讯作者：
张勇
中科院分区：
文献类型：
--
作者：
姜宁;薄海;宋超;郭晶晶;赵斐;冯红;丁虎;吉力立;张勇
摘要目的：帕金森病（Parkinson disease，PD）在老年人中发病率和危险性较高.然而，根本原因尚不清楚。1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）小鼠由于其PD样症状在一定程度上是研究PD相关问题的有用工具。该研究旨在确定是否以及衰老过程中的哪些事件与老年人对MPTP的脆弱性增加有关。方法：腹腔注射MPTP建立MPTP小鼠模型，对照组注射生理盐水。将不同月龄的小鼠分为6组：4月龄对照组、4月龄MPTP组、8月龄对照组、8月龄MPTP组、15月龄对照组和15月龄MPTP组。评估每只小鼠的行为能力和病理学。测定线粒体功能并比较各组间的差异。Western blotting分析线粒体融合/分裂相关蛋白和自噬蛋白。结果：老年动物行为学和病理学损害较青年动物严重。然后，我们揭示了衰老与一些线粒体功能的退化，融合/分裂的平衡失调以及自噬蛋白活性降低有关。更重要的是，老年人的线粒体比年轻人更容易受到MPTP治疗的影响，这可能导致老年人对MPTP的风险和脆弱性增加。结论：我们确定了MPTP小鼠衰老过程中的一些变化，这些变化可能与MPTP的耐受性和脆弱性有关，这将为未来制定适当的干预措施以降低脆弱性或减缓老年人PD的进展提供重要指导。
Abstract Objective: The risk and vulnerability of Parkinson disease (PD) are especially high in the elderly. However, the underlying causes are unknown. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice are useful tools to some extent for investigating PD-related problems due to their PD-like symptoms. The study is aimed to determine whether and what mitochondrial-events during aging are related with the increased vulnerability of the elderly to MPTP. Methods: The MPTP mice were established by intraperitoneal injection of MPTP, control animals were injected with saline. Mice of different ages were divided into six groups: 4-month old control group, 4-month old MPTP group, 8-month old control group, 8-month old MPTP group, 15-month old control group, and 15-month old MPTP group. The behavior ability and pathology were assessed for each mouse. Mitochondrial functions were measured and compared among different groups. Mitochondrial fusion/fission-related proteins and autophagic proteins were analyzed by western blotting. Results: The elder animals were impaired more severely in behavior and pathology than the young ones. Then, we revealed that aging is associated with the degeneration of several mitochondrial functions, disturbed balance of fusion/fission as well as decreased activity of autophagic proteins. More importantly, mitochondria in the elderly are more vulnerable to MPTP treatment than that in the young, which may contribute to the increased risk and vulnerability of the elderly to MPTP. Conclusion: We identified several changes of mitochondrial-events with aging MPTP mice that could be related to the MPTP susceptivity and vulnerability, which would provide significant instructions for future in developing proper interventions that lower the vulnerability, or slow the progression of PD in the elderly.
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影响因子：
4.8
作者：
A. Lockwood
通讯作者：
A. Lockwood
DOI：
10.1097/01.nrl.0000215782.78763.fa
发表时间：
2006-07
期刊：
The Neurologist
影响因子：
--
作者：
D. Silver
通讯作者：
D. Silver
DOI：
10.1056/nejmoa033447
发表时间：
2004-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
S. Fahn;D. Oakes;I. Shoulson;K. Kieburtz;A. Rudolph;A. Lang;C. Olanow;C. Tanner;K. Marek
通讯作者：
S. Fahn;D. Oakes;I. Shoulson;K. Kieburtz;A. Rudolph;A. Lang;C. Olanow;C. Tanner;K. Marek
影响因子：
7.4
作者：
Jiang, Ning;Zhang, Guizhong;Zhang, Yong
通讯作者：
Zhang, Yong
影响因子：
3.3
作者：
Lores-Arnaiz, S.;Bustamante, J.
通讯作者：
Bustamante, J.