title: Gene responses in the central nervous system of zebrafish embryos exposed to the neurotoxicant methyl mercury.
abstract: Methyl mercury (MeHg) is a neurotoxicant with adverse effects on the development of the nervous system from fish to man. Despite a detailed understanding of the molecular mechanisms by which MeHg affects cellular homeostasis, it is still not clear how MeHg causes developmental neurotoxicity. We performed here a genome-wide transcriptional analysis of MeHg-exposed zebrafish embryos and combined this with a whole-mount in situ expression analysis of 88 MeHg-affected genes. The majority of the analyzed genes showed tissue- and region-restricted responses in various organs and tissues. The genes were linked to gene ontology terms like oxidative stress, transport and cell protection. Areas even within the central nervous system (CNS) are affected differently resulting in distinct cellular stress responses. Our study revealed an unexpected heterogeneity in gene responses to MeHg exposure in different tissues and neuronal subregions, even though the known molecular action of MeHg would predict a similar burden of exposed cells. The overall structure of the developing brain of MeHg-exposed embryos appeared normal, suggesting that the mechanism leading to differentiation of the CNS is not overtly affected by exposure to MeHg. We propose that MeHg disturbs the function of the CNS by disturbing the cellular homeostasis. As these cellular stress responses comprise genes that are also involved in normal neuronal activity and learning, MeHg may affect the developing CNS in a subtle manner that manifests itself in behavioral deficits.
authors: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors: Nga Yu
authors: NY
authors: Ho
authors: Lixin
authors: L
authors: Yang
authors: Jessica
authors: J
authors: Legradi
authors: Olivier
authors: O
authors: Armant
authors: Masanari
authors: M
authors: Takamiya
authors: Sepand
authors: S
authors: Rastegar
authors: Uwe
authors: U
authors: Strähle
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016000:Cluster Analysis; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism*; D004781:Environmental Exposure; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D063990:Gene Ontology; D017403:In Situ Hybridization; D008767:Methylmercury Compounds / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*
chemical_list: D008767:Methylmercury Compounds; D009498:Neurotoxins