title: Study of the chlorpyrifos neurotoxicity using neural differentiation of adipose tissue-derived stem cells.
abstract: Chlorpyrifos (CPF) is the most commonly used organophosphorus insecticide which causes neurodevelopmental toxicity. So far, animals have been used as ideal models for neurotoxicity studies, but working with animals is very expensive, laborious, and ethically challenging. This has encouraged researchers to seek alternatives. During recent years, several studies have reported successful differentiation of embryonic and adult stem cells to neurons. This has provided an excellent model for neurotoxicologic studies. In this study, neural differentiation of mouse adipose tissue-derived stem cells (ADSCs) was used as an in vitro model for investigation of CPF neurotoxicity. For this purpose, mouse ADSCs were cultured in a medium containing knockout serum replacement and were treated with different concentrations of CPF at several stages of differentiation. Cytotoxic effect of CPF and the expression of neuron-specific genes and proteins were studied in the differentiating ADSCs. Furthermore, the activity of acetylcholinesterase was assessed by Ellman assay at different stages of differentiation. This study showed that up to 500 μM CPF did not alter viability of the undifferentiated ADSCs, whereas viability of the differentiating cells decreased with 500 μM CPF. CPF upregulated the expression of some neuron-specific genes and seemed to decrease the number of β-tubulin III and MAP2 proteins-expressing cells. There was no detectable acetylcholine esterase activity in differentiated ADSCs. In summary, it was shown that CPF treatment can decrease the viability of ADSC-derived neurons and dysregulate the expression of some neuronal markers through acetylcholinesterase-independent mechanisms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1510-1519, 2016.
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mohammad Hadi
authors.initials: MH
authors.lastname: Zarei
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Soodi
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Qasemian-Lemraski
authors.affiliation: Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Emad
authors.initials: E
authors.lastname: Jafarzadeh
authors.affiliation: Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. mftaha@nigeb.ac.ir.
authors.forename: Masoumeh Fakhr
authors.initials: MF
authors.lastname: Taha
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004390:Chlorpyrifos / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis; D013234:Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology
chemical_list: D007306:Insecticides; D012333:RNA, Messenger; D000110:Acetylcholinesterase; D004390:Chlorpyrifos
keywords: ADSC; chlorpyrifos; differentiation; neuron; neurotoxicity