L-theanine, a Component of Green Tea Prevents 3-Nitropropionic Acid (3-NP)-Induced Striatal Toxicity by Modulating Nitric Oxide Pathway
L-theanine, a Component of Green Tea Prevents 3-Nitropropionic Acid (3-NP)-Induced Striatal Toxicity by Modulating Nitric Oxide Pathway
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DOI：
10.1007/s12035-016-9822-5
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发表时间：
2017-04-01
影响因子：
5.1
通讯作者：
Kumar, Puneet
中科院分区：
文献类型：
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作者：
Jamwal, Sumit;Kumar, Puneet
L-茶氨酸是一种独特的氨基酸，它能很容易地穿过血脑屏障，对神经退行性疾病包括亨廷顿病（HD）具有神经保护作用。HD的特征在于GABA能中型多棘神经元的选择性丧失。3-硝基丙酸（3-NP）在大鼠纹状体中诱导一系列HD样神经病理学，并被广泛用作研究HD的实验工具。因此，本研究旨在研究L-茶氨酸对3-NP所致纹状体毒性的影响，并探讨其可能的机制。大鼠给予3-NP 21天。在3-NP治疗前1小时每天给予一次L-茶氨酸，持续21天，并给予L-NAME（10 mg/kg，i. p.），NO抑制剂和L-精氨酸（50 mg/kg; i. p.），NO前体在L-茶氨酸处理之前1小时施用。每周进行体重和行为学观察。在第22天，处死动物，分离纹状体进行生化（LPO、GSH和亚硝酸盐）、促炎细胞因子和神经化学分析。3-NP处理显著改变了体重、自发活动、运动协调、线粒体复合物-II活性、氧化防御、促炎介质和纹状体神经递质水平。L-茶氨酸预处理（25和50 mg/kg/天，p.o.）显着阻止了这些改变。此外，L-NAME与L-茶氨酸（25 mg/kg/天，p.o.）显著增强L-茶氨酸（25 mg/kg/day，p.o.）而L-精氨酸与L-茶氨酸（50 mg/kg/天，p.o.）显著改善L-茶氨酸（50 mg/kg/天，p.o.）的保护作用。L-茶氨酸的神经保护潜力涉及抑制有害的一氧化氮产生和预防纹状体中神经递质的改变。
L-theanine is unique amino acid which readily crosses blood brain barrier and possesses neuroprotective potential against neurodegenerative disorders including Huntington disease (HD). HD is characterized by selective loss of GABAergic medium spiny neurons. 3-nitropropionic acid (3-NP) induces a spectrum of HD-like neuropathology in rat striatum and widely used as experimental tool to study HD. Therefore, the present study was intended to investigate the effect of L-theanine against 3-NP-induced striatal toxicity and to explore its possible mechanism. Rats were administered with 3-NP for 21 days. L-theanine was given once a day, 1 h prior to 3-NP treatment for 21 days and L-NAME (10 mg/kg, i.p.), NO inhibitor and L-arginine (50 mg/kg; i.p.), NO precursor were administered 1 h prior to L-theanine treatment. Body weight and behavioral observation were made on weekly basis. On the 22nd day, animals were sacrificed, and the striatum was isolated for biochemical (LPO, GSH, and nitrite), pro-inflammatory cytokines and neurochemical analysis. 3-NP treatment significantly altered body weight, locomotor activity, motor coordination, mitochondrial complex-II activity, oxidative defense, pro-inflammatory mediators, and striatal neurotransmitters level. L-theanine pre-treatment (25 and 50 mg/kg/day, p.o.) significantly prevented these alterations. In addition, concurrent treatment of L-NAME with L-theanine (25 mg/kg/day, p.o.) significantly enhanced protective effect of L-theanine (25 mg/kg/day, p.o.) whereas concurrent treatment of L-arginine with L-theanine (50 mg/kg/day, p.o.) significantly ameliorated the protective effect of L-theanine (50 mg/kg/day, p.o.). The neuroprotective potential of L-theanine involves inhibition of detrimental nitric oxide production and prevention of neurotransmitters alteration in the striatum.