title: Trimethyltin chloride inhibits neuronal cell differentiation in zebrafish embryo neurodevelopment.
abstract: Trimethyltin chloride (TMT) is a neurotoxicant widely present in the aquatic environment, primarily from effluents of the plastic industry. It is known to cause acute neuronal death in the limbic-cerebellar system, particularly in the hippocampus. However, relatively few studies have estimated the effects of TMT toxicity on neurodevelopment. In this study, we confirmed the dose-dependent effects of TMT on neurodevelopmental stages through analysis of morphological changes and fluorescence assays using HuC-GFP and olig2-dsRed transgenic zebrafish embryos. In addition, we analyzed the expression of genes and proteins related to neurodevelopment. Exposure of embryos to TMT for 4 days post fertilization (dpf) elicited a concentration-related decrease in body length and increase in axial malformation. TMT affected the fluorescent CNS structure by decreasing pattern of HuC-GFP and olig2-dsRed transgenic zebrafish. In addition, it significantly modulated the expression patterns of Sonic hedgehog a (Shha), Neurogenin1 (Ngn1), Embryonic lethal abnormal vision like protein 3 (Elavl3), and Glial fibrillary acidic protein (Gfap). The overexpression of Shha and Ngn1, and downregulation of Elavl3 and Gfap, indicate repression of proneural cell differentiation. Our study demonstrates that TMT inhibits specific neurodevelopmental stages in zebrafish embryos and suggests a possible mechanism for the toxicity of TMT in vertebrate neurodevelopment.
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: C-Yoon
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Juha
authors.initials: J
authors.lastname: Song
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Hanseul
authors.initials: H
authors.lastname: Oh
authors.affiliation: Department of Biology, , Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: pjhak@snu.ac.kr.
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D000067778:ELAV-Like Protein 3 / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; D007814:Larva; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000494:pharmacology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000067778:ELAV-Like Protein 3; D005904:Glial Fibrillary Acidic Protein; D053823:Hedgehog Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D014298:Trimethyltin Compounds; D029961:Zebrafish Proteins; C512773:Olig2 protein, mouse; C524053:Shha protein, zebrafish; C088635:elavl3 protein, zebrafish; C486337:neurog1 protein, zebrafish; C040533:trimethyltin chloride
keywords: Gene expression; Neurotoxicity; Trimethyltin chloride; Zebrafish