The influence of clozapine treatment and other antipsychotics on the 18 kDa translocator protein, formerly named the peripheral-type benzodiazepine receptor, and steroid production
The influence of clozapine treatment and other antipsychotics on the 18 kDa translocator protein, formerly named the peripheral-type benzodiazepine receptor, and steroid production
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DOI：
10.1016/j.euroneuro.2007.04.005
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发表时间：
2008-01-01
影响因子：
5.6
通讯作者：
Gavish, Moshe
中科院分区：
文献类型：
--
作者：
Danovich, Lena;Veenman, Leo;Gavish, Moshe
研究表明，非典型抗精神病药物氯氮平会增加大鼠大脑中神经类固醇四氢孕酮的水平。 18 kDa 易位蛋白 (TSPO)，以前称为外周型苯二氮卓受体，已被证明参与外周类固醇生成组织以及大脑神经胶质细胞中的类固醇生物合成过程。在当前的研究中，我们研究了氯氮平和其他抗精神病药物（硫利达嗪、舒必利和利培酮）长期治疗对细胞培养物和大鼠组织中 TSPO 结合的影响。氯氮平显着增加了 C6 大鼠神经胶质瘤细胞和 MA-10 小鼠 Leydig 肿瘤细胞中的 TSPO 结合密度，而抗精神病药物舒必利对两种细胞系中的 TSPO 结合密度没有影响。此外，氯氮平（而非舒必利）显着增加 MA-10 Leydig 肿瘤细胞的孕酮合成。在一项动物实验中，雄性 Sprague-Dawley 大鼠接受氯氮平 (20 mg/kg)、利培酮 (0.5 mg/kg)、硫利达嗪 (20 mg/kg) 或舒必利 (20 mg/kg) 治疗 21 天，然后停药 7 天。氯氮平诱导大脑和外周类固醇生成组织中 TSPO 结合显着增加，而其他抗精神病药物对 TSPO 结合没有表现出如此明显的影响。我们的结果表明 TSPO 可能参与氯氮平对类固醇生成的调节。 (C) 2007 Elsevier B.V. 和 ECNP。版权所有。
It has been shown that the atypical antipsychotic drug clozapine increases the levels of the neurosteroid allopregnanolone in the rat brain. The 18 kDa translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, has been demonstrated to be involved in the process of steroid biosynthesis, in peripheral steroidogenic tissues as well as in glia cells in the brain. In the current study, we investigated the influence of chronic treatment with clozapine and other antipsychotics (thioridazine, sulpiride and risperidone) on TSPO binding in cell cultures and rat tissues. Clozapine significantly increased TSPO binding density in C6 rat glioma cells and in MA-10 mouse Leydig tumor cells, while the antipsychotic sulpiride had no effect on TSPO binding density in both cell lines. In addition, clozapine, but not sulpiride, significantly increased progesterone synthesis by MA-10 Leydig tumor cells. In an animal experiment, mate Sprague-Dawley rats were treated with clozapine (20 mg/kg), risperidone (0.5 mg/kg), thioridazine (20 mg/kg), or sulpiride (20 mg/kg) for 21 days, followed by 7 days of withdrawal. Clozapine induced significant increases in TSPO binding in brain and peripheral steroidogenic tissues, whereas the other antipsychotics did not show such pronounced effects on TSPO binding. Our results suggest that TSPO may be involved in the modulation of steroidogenesis by clozapine. (C) 2007 Elsevier B.V. and ECNP. All rights reserved.