Long Yi-Guo, Wang Ya-Nan, Chen Jia, Jiang Su-Fen, Nordberg Agneta, Guan Zhi-Zhong
Department of Pathology, Guiyang Medical College, Guizhou, PR China.
Neurotoxicol Teratol. 2002 Nov-Dec;24(6):751-7. doi: 10.1016/s0892-0362(02)00273-8.
In order to investigate the molecular mechanism(s) underlying brain dysfunction caused by chronic fluorosis, neuronal nicotinic acetylcholine receptors (nAChRs) in the brain of rats receiving either 30 or 100 ppm fluoride in their drinking water for 7 months were analyzed in the present study employing ligand binding and Western blotting. There was a significant reduction in the number of [3H]epibatidine binding sites in the brain of rats exposed 100 ppm of fluoride, but no alteration after exposed to 30 ppm. On the other hand, the number of [125I]alpha-BTX binding sites was significantly decreased in the brains of rats exposed to both levels of fluoride. Western blotting revealed that the level of the nAChR alpha4 subunit protein in the brains of rats was significantly lowered by exposure to 100 ppm, but not 30 ppm fluoride; whereas the expression of the alpha7 subunit protein was significantly decreased by both levels of exposure. In contrast, there was no significant change in the level of the beta2 subunit protein in the brains of rats administered fluoride. Since nAChRs play major roles in cognitive processes such as learning and memory, the decrease in the number of nAChRs caused by fluoride toxicity may be an important factor in the mechanism of brain dysfunction in the disorder.
为了探究慢性氟中毒导致脑功能障碍的分子机制，本研究采用配体结合和蛋白质印迹法，分析了饮用含30或100 ppm氟的水7个月的大鼠脑中的神经元烟碱型乙酰胆碱受体（nAChRs）。暴露于100 ppm氟的大鼠脑中，[3H]埃博霉素结合位点数量显著减少，但暴露于30 ppm氟后无变化。另一方面，暴露于两种氟水平的大鼠脑中，[125I]α-银环蛇毒素结合位点数量均显著减少。蛋白质印迹显示，暴露于100 ppm氟而非30 ppm氟可显著降低大鼠脑中nAChR α4亚基蛋白水平；而两种暴露水平均显著降低α7亚基蛋白表达。相比之下，给予氟的大鼠脑中β2亚基蛋白水平无显著变化。由于nAChRs在学习和记忆等认知过程中起主要作用，氟中毒导致的nAChRs数量减少可能是该疾病脑功能障碍机制中的一个重要因素。
