In vivo and in vitro synthesis, release, and uptake of [3-H]-dopamine in mouse striatal slices after in vivo exposure to chlordecone.

K Fujimori, H Benet, H M Mehendale, I K Ho
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引用次数: 10

Abstract

Effects of treatment of mice with chlordecone (25 mg/kg/d) on striatal dopaminergic activities such as synthesis, turnover, uptake, and release were investigated in vivo and in vitro. In mice receiving chlordecone for five days, there were no significant changes in in vivo dopamine (DA) synthesis and turnover in striatum and in vitro [3-H]-dopamine uptake and K+-stimulated [3-H]-dopamine release in striatal slices. In mice receiving chlordecone for eight days, the in vivo synthesis of [3-H]-dopamine from [3-H]-tyrosine in striatum was slightly inhibited and the in vitro [3-H]-dopamine synthesis in striatal slices was significantly decreased. Furthermore, both uptake and K+-stimulated release of [3-H]-dopamine from striatal slices were significantly reduced. The turnover rate of newly synthesized [3-H]-dopamine from [3-H]-tyrosine in striatal slices was unchanged after eight consecutive days of chlordecone administration. These results suggest that chlordecone may cause impairments in pre- and/or postsynaptic membranes of dopaminergic neurons which modulate motor function.

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小鼠体内暴露于十氯酮后纹状体切片中[3-H]-多巴胺的体内和体外合成、释放和摄取
研究了十氯酮(25 mg/kg/d)对小鼠纹状体多巴胺能合成、转化、吸收和释放等活性的影响。十氯酮给药5天后,纹状体体内多巴胺(DA)合成和转换以及体外纹状体切片[3-H]-多巴胺摄取和K+刺激[3-H]-多巴胺释放均无显著变化。十氯酮给药8天后,纹状体[3-H]-酪氨酸在体内合成[3-H]-多巴胺受到轻微抑制,纹状体切片体外合成[3-H]-多巴胺明显减少。此外,纹状体切片对[3-H]-多巴胺的摄取和K+刺激释放均显著减少。十氯酮连续给药8天后纹状体切片中[3-H]-酪氨酸新合成的[3-H]-多巴胺的周转率没有变化。这些结果表明,十氯酮可能导致多巴胺能神经元突触前膜和/或突触后膜的损伤,多巴胺能神经元调节运动功能。
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