Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, LiaoNing 116044, PR China.
Neuroscience. 2013 Jun 25;241:52-8. doi: 10.1016/j.neuroscience.2013.03.014. Epub 2013 Mar 19.
Little is known about the influence of arsenic (As) exposure on monoamine neurotransmitters and the underlying mechanisms, although arsenic toxicity on the central nervous system has been well documented. In the present study, the levels of norepinephrine (NE), dopamine (DA), and 5-HT were determined by high performance liquid chromatography in the cerebrum and cerebellum of mice exposed to 1, 2 and 4 ppm As2O3 through drinking water for 60 days. The ultra-structural change of vesicles in the synapses of mice brains was observed by transmission electron microscopy; the mRNA expressions of dopamine beta hydroxylase (DBH), tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) as NE, DA and 5-HT synthetases were quantitatively assessed by real time reverse transcription-polymerase chain reaction. It was shown that the concentrations of NE, DA and 5-HT in the cerebrum or cerebellum of mice exposed to As were significantly lower than those in the control group. The number of synaptic vesicles significantly decreased in the brain of mice exposed to As. Moreover, the expressions of TH, TPH and DBH genes were significantly lower in the brains of mice exposed to As than those in the controls. These results suggested that subchronic exposure to As might decrease the concentrations of the three monoamine neurotransmitters in the mouse brain and downregulate TH, TPH and DBH gene expressions. It was also indicated that the decreased concentrations of the three monoamine neurotransmitters in the brain might be related to the down-regulated gene expressions of these synthetases by As.
目前对于砷暴露对单胺类神经递质的影响及其潜在机制知之甚少,尽管砷对中枢神经系统的毒性已有大量记载。在本研究中,通过饮水方式使小鼠暴露于 1、2 和 4 ppm As2O3 中 60 天,采用高效液相色谱法测定其大脑皮层和小脑组织中去甲肾上腺素(NE)、多巴胺(DA)和 5-羟色胺(5-HT)的含量。利用透射电子显微镜观察突触囊泡的超微结构变化;实时逆转录聚合酶链反应定量评估多巴胺β羟化酶(DBH)、酪氨酸羟化酶(TH)和色氨酸羟化酶(TPH)的 mRNA 表达,作为 NE、DA 和 5-HT 的合成酶。结果表明,暴露于砷的小鼠大脑或小脑组织中的 NE、DA 和 5-HT 浓度明显低于对照组。暴露于砷的小鼠脑内突触囊泡数量明显减少。此外,暴露于砷的小鼠脑内 TH、TPH 和 DBH 基因的表达明显低于对照组。这些结果表明,亚慢性砷暴露可能会降低小鼠大脑中这三种单胺类神经递质的浓度,并下调 TH、TPH 和 DBH 基因的表达。同时也表明,脑内三种单胺类神经递质浓度的降低可能与砷对这些合成酶基因表达的下调有关。