Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model.
Metabolic Disturbances in the Striatum and Substantia Nigra in the Onset and Progression of MPTP-Induced Parkinsonism Model.
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MPTP 诱发的帕金森病模型发病和进展过程中纹状体和黑质的代谢紊乱
DOI：
10.3389/fnins.2018.00090
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发表时间：
2018
影响因子：
4.3
通讯作者：
Yan Z
中科院分区：
文献类型：
--
作者：
Lu Y;Zhang X;Zhao L;Yang C;Pan L;Li C;Liu K;Bai G;Gao H;Yan Z
代谢紊乱与帕金森病（PD）的发病机制有关，而与PD发病和进展相关的动态变化尚不清楚。本研究通过检测1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的帕金森病模型从开始到发展过程中代谢产物的动态变化，以阐明其潜在的代谢机制。在注射MPTP后1、7和21天，使用离体1H核磁共振（NMR）光谱测量小鼠纹状体和黑质（SN）中的代谢物变化。代谢组学分析显示，在不同时间点，PD和对照小鼠之间的总体代谢物明显分离。纹状体中的谷氨酸（Glu）在诱导PD第1天小鼠显著升高，持续至第21天。诱导PD小鼠纹状体内NAA在第1天和第7天升高，但在第21天无显著差异。诱导PD第1天小鼠纹状体中的肌肌醇（mI）和牛磺酸（Tau）也受到干扰。此外，谷氨酸-谷氨酰胺循环中的关键酶在PD小鼠中显著增加。这些结果表明，诱导PD小鼠的神经元丢失和运动功能障碍可能与过度活跃的谷氨酸-谷氨酰胺循环和膜代谢改变有关。
Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD), while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo 1H nuclear magnetic resonance (NMR) spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN) of mice at 1, 7, and 21 days after injection of MPTP. Metabolomic analysis revealed a clear separation of the overall metabolites between PD and control mice at different time points. Glutamate (Glu) in the striatum was significantly elevated at induction PD day 1 mice, which persisted to day 21. N-acetylaspartate (NAA) increased in the striatum of induction PD mice on days 1 and 7, but no significant difference was found in striatum on day 21. Myo-Inositol (mI) and taurine (Tau) were also disturbed in the striatum in induction PD day 1 mice. Additionally, key enzymes in the glutamate-glutamine cycle were significantly increased in PD mice. These findings suggest that neuron loss and motor function impairment in induction PD mice may be linked to overactive glutamate-glutamine cycle and altered membrane metabolism.
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影响因子：
14.8
作者：
Jackson-Lewis, Vernice;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
4.3
作者：
Lewerenz J;Maher P
通讯作者：
Maher P
影响因子：
11
作者：
Hatano, Taku;Saiki, Shinji;Hattori, Nobutaka
通讯作者：
Hattori, Nobutaka
影响因子：
168.9
作者：
Kalia, Lorraine V.;Lang, Anthony E.
通讯作者：
Lang, Anthony E.
影响因子：
3.5
作者：
Di Leo, MAS;Santini, SA;Ghirlanda, G
通讯作者：
Ghirlanda, G