Del Pino Javier, Zeballos Garbriela, Anadon María José, Capo Miguel Andrés, Díaz María Jesús, García Jimena, Frejo María Teresa
Department of Toxicology and Pharmacology, Veterinary School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, Madrid 28040, Spain.
Department of Toxicology and Legal Medicine, Medical School, Complutense University of Madrid, Madrid 28041, Spain.
Toxicology. 2014 Nov 5;325:151-9. doi: 10.1016/j.tox.2014.09.004. Epub 2014 Sep 6.
Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases.
镉是一种环境污染物，令人担忧，因为它可在生物体内大量富集，对包括神经系统在内的多种器官造成严重损害，而神经系统是受影响最严重的器官之一。据报道，镉会导致学习和记忆功能障碍以及类似阿尔茨海默病的症状，但其机制尚不清楚。另一方面，中枢神经系统（CNS）中的胆碱能系统与学习和记忆调节有关，据报道镉会影响胆碱能传递，还可在外周水平对胆碱能系统诱导选择性毒性，导致胆碱能神经元丧失，如果在中枢水平发生这种情况，可能解释镉对学习和记忆过程的影响。本研究旨在探讨镉对中枢神经系统胆碱能系统诱导的选择性神经毒性。为此，我们在基底前脑区域评估了镉对神经元活力的毒性作用以及与NS56胆碱能小鼠隔区细胞系相关的胆碱能机制。本研究证明，镉对胆碱能神经元的乙酰胆碱酯酶（AChE）诱导更明显但非选择性的细胞死亡。此外，MTT和LDH检测显示NS56细胞的细胞活力呈剂量依赖性下降。用ACh处理SN56细胞不能逆转镉诱导的细胞活力降低，但针对AChE的siRNA转染可部分降低细胞活力。我们目前的结果为镉对神经元功能和活力产生有害影响的机制以及镉在神经退行性疾病发病机制中的可能相关性提供了新的认识。
