Journal
NEUROTOXICOLOGY AND TERATOLOGY
Volume 54, Issue -, Pages 29-35Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ntt.2015.12.003
Keywords
Trimethyltin chloride; Zebrafish; Neurotoxicity; Gene expression
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Funding
- Brain Korea 21 PLUS Program for Creative Veterinary Science Research
- Research Institute for Veterinary Science College of Veterinary Medicine of Seoul National University
- National Research Foundation of Korea (NRF) [2015R1C1A1A02037047]
- National Research Foundation of Korea [2015R1C1A1A02037047] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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), Neurogeninl (Ngn1), Embryonic lethal abnormal vision like protein 3 (ElavI3), and Glial fibrillary acidic protein (Gfap). The overexpression of Shha and Ngn1, and down regulation 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. (C) 2015 Elsevier Inc. All rights reserved.
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