Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease
Ketogenic diet protects dopaminergic neurons against 6-OHDA neurotoxicity via up-regulating glutathione in a rat model of Parkinson's disease
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DOI：
10.1016/j.brainres.2009.06.060
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Liu, Shuwei
中科院分区：
文献类型：
--
作者：
Cheng, Baohua;Yang, Xinxin;Liu, Shuwei
高脂肪生酮饮食（KD）导致血酮体（KB）水平升高，被用于治疗难治性儿童癫痫发作已有80多年的历史。最近的报道表明，KD、KB及其组分（d - β -羟基丁酸酯、乙酰乙酸酯和丙酮）对急性和慢性神经系统疾病具有神经保护作用。在我们目前的工作中，我们使用尼氏染色和酪氨酸羟化酶（TH）免疫组织化学检测了KD是否保护黑质（SN）多巴胺能神经元免受6-羟基多巴胺（6-OHDA）的神经毒性。同时测定纹状体多巴胺（DA）及其代谢物二羟基苯乙酸（DOPAC）和同型香草酸（HVA）含量。为了阐明其机制，我们还测量了纹状体谷胱甘肽（GSH）的水平。我们的数据显示，与正常饮食（ND）的大鼠相比，KD喂养的大鼠在纹状体内注射6-OHDA后，Nissl和th阳性神经元增加，DA及其代谢物DOPAC也增加。而HVA没有明显变化。GSH的变化与DA有明显相似。我们得出结论，KD对6-OHDA神经毒性具有神经保护作用，在此期间谷胱甘肽发挥了重要作用。(C) 2009 Elsevier B.V.版权所有
The high-fat ketogenic diet (KD) leads to an increase of blood ketone bodies (KB) level and has been used to treat refractory childhood seizures for over 80 years. Recent reports show that KD, KB and their components (D-beta-hydroxybutyrate, acetoacetate and acetone) have neuroprotective for acute and chronic neurological disorders. in our present work, we examined whether KD protected dopaminergic neurons of substantia nigra (SN) against 6-hydroxydopamine (6-OHDA) neurotoxicity in a rat model of Parkinson's disease (PD) using Nissl staining and tyrosine hydroxylase (TH) immunohistochemistry. At the same time we measured dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. To elucidate the mechanism, we also measured the level of glutathione (GSH) of striatum. Our data Showed that Nissl and TH-positive neurons increased in rats fed with KD compared to rats with normal diet (ND) after intrastriatal 6-OHDA injection, so did DA and its metabolite DOPAC. While HVA had not changed significantly. The change of GSH was significantly similar to DA. We concluded that KD had neuroprotective against 6-OHDA neurotoxicity and in this period GSH played an important role. (C) 2009 Elsevier B.V. All rights reserved.