Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: A cholinesterase dependent mechanism

• Published in: Toxicology (Amsterdam) 2014-11, Vol.325, p.151-159
• Main Authors: Del Pino, Javier, Zeballos, Garbriela, Anadon, María José, Capo, Miguel Andrés, Díaz, María Jesús, García, Jimena, Frejo, María Teresa
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholine - metabolism; Acetylcholine transferase; Acetylcholinesterase; Acetylcholinesterase - metabolism; Animals; Basal forebrain neurons; Cadmium; Cadmium Chloride - toxicity; Cell death; Cell Death - drug effects; Cell Line, Tumor; Central nervous system; Cholinergic Neurons - drug effects; Cholinergic Neurons - enzymology; Cholinergic Neurons - pathology; Cholinergics; Cholinesterases - genetics; Cholinesterases - metabolism; Dose-Response Relationship, Drug; Emergency; Environmental Pollutants - toxicity; Female; Gene Expression Regulation, Enzymologic; GPI-Linked Proteins - metabolism; Learning; Mice; Neurons; Pregnancy; Prosencephalon - drug effects; Prosencephalon - embryology; Prosencephalon - enzymology; Prosencephalon - pathology; Rats, Wistar; RNA Interference; RNA, Messenger - metabolism; Selective neurotoxicity; Toxicology; Transfection; Viability
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2014.09.004

Abstract 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.