title: Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: a cholinesterase dependent mechanism.
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.
authors.affiliation: Department of Toxicology and Pharmacology, Veterinary School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, Madrid 28040, Spain. Electronic address: jdelpino@pdi.ucm.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Del Pino
authors.affiliation: Department of Toxicology and Legal Medicine, Medical School, Complutense University of Madrid, Madrid 28041, Spain.
authors.forename: Garbriela
authors.initials: G
authors.lastname: Zeballos
authors.affiliation: Department of Toxicology and Legal Medicine, Medical School, Complutense University of Madrid, Madrid 28041, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Anadon
authors.affiliation: Department of Toxicology and Pharmacology, Veterinary School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, Madrid 28040, Spain.
authors.forename: Miguel Andrés
authors.initials: MA
authors.lastname: Capo
authors.affiliation: Department of Toxicology and Pharmacology, Veterinary School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, Madrid 28040, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Díaz
authors.affiliation: Department of Pharmacology, Health Sciences School, Alfonso X University, Madrid 28691, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: García
authors.affiliation: Department of Toxicology and Pharmacology, Veterinary School, Complutense University of Madrid, Avda. Puerta de Hierro s/n, Madrid 28040, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Frejo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002802:Cholinesterases / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D011247:Pregnancy; D016548:Prosencephalon / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D014162:Transfection
chemical_list: D004785:Environmental Pollutants; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D000110:Acetylcholinesterase; C548245:Ache protein, mouse; C548246:Ache protein, rat; D002802:Cholinesterases; D019256:Cadmium Chloride; D000109:Acetylcholine
keywords: Acetylcholine; Acetylcholine transferase; Acetylcholinesterase; Basal forebrain neurons; Cadmium; Selective neurotoxicity