A study on the possible roles of brain iron associated with the pathogenesis of neuroleptic-induced tardive dyskinesia

脑铁与抗精神病药引起的迟发性运动障碍发病机制相关的可能作用的研究

• 批准号: 06670967
• 负责人: MORI Norio
• 金额: $ 1.22万
• 依托单位: Fukushima Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670967/
• 关键词: tardive dyskinesia; iron ions; reactive oxygen species; lipid peroxidation; neuroleptics; hydroxyl radical; hydragen peroxide; superoxide anion; 脂質過酸化反応産物; ハロペリドール; Fenton反応; 線条体

One of the serious side effects of neuroleptic therapy is a movement disorder, tardive dyskinesia. In this study, we investigated the possible roles of reactive oxygen species in the pathogenesis of the disorder. The obtained results were as follows.1. Rats were given chronic administration of a neuroleptic haloperidol. Subsequently, the levels of Fe^<2+> and Fe^<3+> in the brain were determined by means of an electron spin resonance (ESR) spectrometry. The result showed no change in both iron ions.2. However, the increase in the hydrogen peroxide and the enhancement of lipid peroxidation were observed.3. An ESR study showed a strong antioxidant effects of Vitamin E,Vitamin C,and Idebenone (Avnan). This result may be important for the next step for the clinical treatment of tardive dyskinesia.4. We developed a new method for the detection of superoxide anion.The results obtained in this study and the newly developed methods should provide a useful information for understanding the detailed mechanisms underlying the neuroleptic-induced tradive dyskinesia.

精神抑制剂治疗的严重副作用之一是运动障碍，迟发性运动障碍。在这项研究中，我们调查了活性氧在疾病的发病机制中可能发挥的作用。主要研究结果如下：1.对大鼠长期给予神经抑制剂氟哌啶醇。随后，通过电子自旋共振（ESR）光谱法测定脑中Fe^<2+>和Fe^<3+>的水平。结果表明，两种铁离子均无变化.但过氧化氢含量增加，脂质过氧化作用增强. ESR研究表明，维生素E、维生素C和艾地苯醌（Avnan）具有很强的抗氧化作用。这一结果可能对迟发性运动障碍的下一步临床治疗具有重要意义.我们建立了一种新的超氧阴离子检测方法，本研究的结果和新建立的方法为深入了解抗精神病药引起的运动障碍的详细机制提供了有用的信息。

项目成果

Matsumoto H,et al: "The level of free irons in the brain after subchronic parenteral administration of haloperidol in rats,demons trated by ESR spectroscopy" Magnetic Resonance in Medicine. 6. 258-260 (1995)

Matsumoto H 等人：“大鼠亚慢性肠外注射氟哌啶醇后大脑中游离铁的水平，通过 ESR 光谱法证实”《医学磁共振》。

Matsumoto S,et al: "Effects of Idebenone on the metabolic fate of an intravenously given nitroxide radical in rats:a study by means of L-band ESR technique" Magnetic Resonance in Medicine. 6. 181-183 (1995)

Matsumoto S 等人：“艾地苯醌对大鼠静脉内给予硝基氧自由基代谢命运的影响：通过 L 波段 ESR 技术进行的研究”《医学磁共振》。

Matsumoto H, et al: "The level of free iron ions in the brain after subcheonic parenteral administration of haloperidol in rats, demonstrated by electron spin resonance spectroscopy" Magnetic Resonance in Medicine. 6. 258-260 (1995)

Matsumoto H 等人：“通过电子自旋共振波谱法证实大鼠肠外注射氟哌啶醇后大脑中游离铁离子的水平”《医学磁共振》。

Yokoyama Hidekatsu, et al: "Microelectrode-detected electron spin resonance (MEDESR) signals of free radicals in electrolyte solutions" Chemistry Letters. 919-220 (1995)

Yokoyama Hidekatsu 等人：“微电极检测电解质溶液中自由基的电子自旋共振 (MEDESR) 信号”化学快报。

Matsumoto,H., Nakagawa,K., et al: "The level of free iron ions in the brain after subchroric parenteral adnuristration of heloperidol in rats, demonstrated by electron spin resorance spectroscopy" Magnetic Resonance In Medicine. 6. 258-260 (1995)

Matsumoto,H.、Nakakawa,K. 等人：“通过电子自旋共振光谱法证明大鼠亚慢性肠外注射氯哌啶醇后大脑中游离铁离子的水平”《医学磁共振》。