Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins
Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins
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DOI：
10.1016/j.brainres.2004.11.019
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发表时间：
2005-02-08
期刊：
影响因子：
2.9
通讯作者：
Ohta, S
中科院分区：
文献类型：
--
作者：
Kotake, Y;Taguchi, R;Ohta, S
1-甲基-1，2，3，4-四氢异喹啉（1-Methyl-1，2，3，4-tetrahydroisoquinoline，1 MeTIQ）是一种内源性脑胺，帕金森病患者脑内1 MeTIQ含量较正常对照组降低。有一些证据表明，1 MeTIQ可以保护多巴胺能神经元免受功能障碍，例如帕金森病中出现的功能障碍。在这项研究中，我们研究了1 MeTIQ对4种多巴胺能神经毒素，1-甲基-4-苯基吡啶离子，6-羟基多巴胺，鱼藤酮，1-苄基-1，2，3，4-四氢异喹啉在培养的大鼠中脑神经元的神经保护作用。1 MeTIQ对所有这些毒素都具有神经保护作用。此外，（R）-1MeTIQ具有神经保护作用，而（S）-1MeTIQ几乎没有作用，表明该作用是立体选择性的。1 MeTIQ的保护作用在中脑神经元中最为有效，尤其是在酪氨酸羟化酶阳性神经元。1 MeTIQ对多巴胺受体无亲和力，不影响鱼藤酮、1-甲基-4-苯基吡啶离子和1-苄基-1，2，3，4-四氢异喹啉对线粒体呼吸复合物I的抑制作用。这些结果提高了1 MeTIQ间接作为抗氧化剂的可能性，例如诱导抗氧化酶，因为所有这四种神经毒素都可以共同负担氧化应激。这是第一份证实1 MeTIQ在培养的神经元水平上具有保护作用的报告，它可能具有开发治疗帕金森病的新药的先导化合物的潜力。(C)2005 Elsevier B.V保留所有权利。
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous brain amine and its content in parkinsonian brain is decreased compared with that in control brain. There is some evidence that 1MeTIQ protects dopaminergic neurons against dysfunction such as that seen in Parkinson's disease. In this study, we examined the neuroprotective effect of 1MeTIQ against four dopaminergic neurotoxins, 1-methyl-4-phenylpyridinuim ion, 6-hydroxydopamine, rotenone, and 1-benzyl-1,2,3,4-tetrahydroisoquinoline, in cultured rat mesencephalic neurons. 1MeTIQ exerted neuroprotective action against all these toxins. Furthermore, (R)-1MeTIQ was neuroprotective, while (S)-1MeTIQ had little effect, indicating that the effect is stereoselective. The protective action of 1MeTIQ was most effective in mesencephalic neurons, especially in tyrosine hydroxylase-positive neurons. 1MeTIQ showed no affinity for dopamine receptors and did not influence the inhibition of mitochondrial respiratory complex I by rotenone, 1-methyl-4-phenylpyridinuim ion, or 1-benzyl-1,2,3,4-tetrahydroisoquinoline. These results raise the possibility that 1MeTIQ indirectly acts as an anti-oxidant such as the induction of anti-oxidative enzymes, because all these four neurotoxins can burden oxidative stress in common. This is the first report to confirm a protective effect of 1MeTIQ at the cultured neuron level, and it may have potential as a lead compound for the development of new agents to treat Parkinson's disease. (C) 2005 Elsevier B.V All rights reserved.