Sepand Rastegar

Publications (31) View all

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  Available from: Sepand Rastegar

  Article: Gene responses in the central nervous system of zebrafish embryos exposed to the neurotoxicant methyl mercury.

  Nga Yu Ho, Lixin Yang, Jessica Legradi, Olivier Armant, Masanari Takamiya, Sepand Rastegar, Uwe Straehle
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  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 analysed 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 behavioural deficits.
  Environmental Science & Technology 03/2013; · 4.80 Impact Factor
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  Available from: Steffen H. Keiter

  Article: DanTox—a novel joint research project using zebrafish (Danio rerio) to identify specific toxicity and molecular modes of action of sediment-bound pollutants

  Steffen Keiter, Sabrina Peddinghaus, Ute Feiler, Britta von der Goltz, Christoph Hafner, Nga Yu Ho, Sepand Rastegar, Jens C. Otte, Richard Ottermanns, Georg Reifferscheid, Uwe Strähle, Thomas Braunbeck, Monika Hammers-Wirtz, Henner Hollert
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  ABSTRACT: IntroductionThe European Water Framework Directive aims to achieve a good ecological and chemical status in surface water of European rivers by the year 2015. Since sediments and particulate matter act as secondary sources for pollutants, applied sediment toxicology is perceived to play a major role for obtaining new knowledge that can contribute to successful attainment of the goal. However, the existing bioassays for sediment toxicity analyses do not provide sufficient data concerning bioavailability of environmental pollutants. In this regard, there is an urgent need to combine sediment contact assays with gene expression analysis to investigate mechanism-specific sediment toxicity. PurposeThe aim of the novel joint research project is to develop a eukaryotic test system, which can be used to investigate the ecotoxicological effects of contaminated sediments on gene expression level (DNA-array and RT-PCR). Current ecotoxicological research customarily involves a battery of bioassays to cover different toxicological endpoints (e.g., teratogenicity, genotoxicity, mutagenicity, Ah-receptor-mediated toxicity, neurotoxicity). In contrast, methods that detect alterations in gene expression offer deeper insight by elucidating how chemical exposure and/or environmental challenge affect multiple metabolic pathways leading to these particular kinds of toxic response. Gene expression profiles reflect the way cells and organisms adapt or respond to a changing environment. ConclusionThe present project aspires to increase the fundamental molecular and physiological knowledge concerning the mode of action of environmental toxicants in zebrafish (Danio rerio). By working with partners from the academic and research institutions as well as from industry and waterway regulations, the success of this basic research-driven joint project in terms of development and implementation of novel sediment toxicity methods will be realized. Keywords Danio rerio -Genomics-Sediments-Toxicity
  Journal of Soils and Sediments 04/2012; 10(4):714-717. · 1.86 Impact Factor
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  Available from: Sepand Rastegar

  Article: Regenerative response following stab injury in the adult zebrafish telencephalon.

  Martin März, Rebecca Schmidt, Sepand Rastegar, Uwe Strähle
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  ABSTRACT: In contrast to mammals, the brain of the adult zebrafish has a remarkable ability to regenerate. In mammals, injuries induce proliferation of astrocytes and oligodendrocyte progenitors contributing to the formation of a glial scar. We analyzed the proliferation of glial cells and microglia in response to stab injury in the adult zebrafish telencephalon: Radial glial markers were up-regulated at the ventricle and co-expressed the proliferation nuclear antigen (PCNA). Microglia and oligodendrocyte progenitors accumulated transiently at the site of lesion. However, we could not find evidence of permanent scar formation. Parenchymal proliferation was almost negligible in comparison to the increase in proliferation at the ventricular zone. This suggests that most of the cellular material for regeneration is derived from regions of constitutive neurogenesis. Remarkably, the proliferative response is almost completely restricted to the lesioned hemisphere indicating that signals inducing regeneration remain mainly confined within the lesioned half of the telencephalon.
  Developmental Dynamics 09/2011; 240(9):2221-31. · 2.54 Impact Factor
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  Article: Zebrafish embryos as an alternative to animal experiments--a commentary on the definition of the onset of protected life stages in animal welfare regulations.

  Uwe Strähle, Stefan Scholz, Robert Geisler, Petra Greiner, Henner Hollert, Sepand Rastegar, Axel Schumacher, Ingrid Selderslaghs, Carsten Weiss, Hilda Witters, Thomas Braunbeck
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  ABSTRACT: Worldwide, the zebrafish has become a popular model for biomedical research and (eco)toxicology. Particularly the use of embryos is receiving increasing attention, since they are considered as replacement method for animal experiments. Zebrafish embryos allow the analysis of multiple endpoints ranging from acute and developmental toxicity determination to complex functional genetic and physiological analysis. Particularly the more complex endpoints require the use of post-hatched eleutheroembryo stages. According to the new EU Directive 2010/63/EU on the protection of animals used for scientific purposes, the earliest life-stages of animals are not defined as protected and, therefore, do not fall into the regulatory frameworks dealing with animal experimentation. Independent feeding is considered as the stage from which free-living larvae are subject to regulations for animal experimentation. However, despite this seemingly clear definition, large variations exist in the interpretation of this criterion by national and regional authorities. Since some assays require the use of post-hatched stages up to 120 h post fertilization, the literature and available data are reviewed in order to evaluate if this stage could still be considered as non-protected according to the regulatory criterion of independent feeding. Based on our analysis and by including criteria such as yolk consumption, feeding and swimming behavior, we conclude that zebrafish larvae can indeed be regarded as independently feeding from 120 h after fertilization. Experiments with zebrafish should thus be subject to regulations for animal experiments from 120 h after fertilization onwards.
  Reproductive Toxicology 06/2011; 33(2):128-32. · 3.23 Impact Factor
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  Available from: Sepand Rastegar

  Article: Expression of the transcription factor Olig2 in proliferating cells in the adult zebrafish telencephalon.

  Martin März, Rebecca Schmidt, Sepand Rastegar, Uwe Strähle
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  ABSTRACT: The telencephalon of the adult zebrafish is highly proliferative: Dividing cells are found along the entire ventricular zone and in the parenchyma. Here, we investigated the relation of proliferating cells in the telencephalic parenchyma to the oligodendrocyte lineage. We find at least three different cell types of the oligodendrocyte lineage (olig2-and sox10-positive) in the parenchyma of the telencephalon: Proliferating progenitors (PCNA-positive), including a subpopulation of slowly dividing progenitors (long term label-retaining), as well as mature oligodendrocytes (Mbp-positive) and presumptive quiescent OPCs (neither Mbp-positive nor proliferating). Furthermore, in the ventricular zone (in and ventral to the RMS), two different subpopulations of olig2-positive cell populations are present. Since these ventricular olig2-positive cells do not express the oligodendrocyte marker sox10, it is not clear whether these cells indeed belong to the oligodendrocyte lineage. Taken together, we detected at least five different classes of olig2-positive cells in the telencephalon of the adult zebrafish.
  Developmental Dynamics 10/2010; 239(12):3336-49. · 2.54 Impact Factor