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Int. J. Mol. Sci. 2017, 18(2), 365;

Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure

Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece
Division of Biomedical Research, Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, 45110 Ιοannina, Greece
BIOBIDE, Paseo Mikeletegi 56, 20009 San Sebastian, Spain
Laboratory of Zoology, Department of Biological Applications and Technologies, University of Ioannina, 45110 Ioannina, Greece
Author to whom correspondence should be addressed.
Academic Editor: Juliette Legler
Received: 27 December 2016 / Revised: 29 January 2017 / Accepted: 2 February 2017 / Published: 9 February 2017
(This article belongs to the Special Issue Zebrafish: A Model for Toxicological Research)
Full-Text   |   PDF [1080 KB, uploaded 9 February 2017]   |  


Microcystins are cyclic heptapeptides that constitute a diverse group of toxins produced by cyanobacteria. One of the most toxic variants of this family is microcystin-LR (MCLR) which is a potent inhibitor of protein phosphatase 2A (PP2A) and induces cytoskeleton alterations. In this study, zebrafish larvae exposed to 500 μg/L of MCLR for four days exhibited a 40% reduction of PP2A activity compared to the controls, indicating early effects of the toxin. Gene expression profiling of the MCLR-exposed larvae using microarray analysis revealed that keratin 96 (krt96) was the most downregulated gene, consistent with the well-documented effects of MCLR on cytoskeleton structure. In addition, our analysis revealed upregulation in all genes encoding for the enzymes of the retinal visual cycle, including rpe65a (retinal pigment epithelium-specific protein 65a), which is critical for the larval vision. Quantitative real-time PCR (qPCR) analysis confirmed the microarray data, showing that rpe65a was significantly upregulated at 50 μg/L and 500 μg/L MCLR in a dose-dependent manner. Consistent with the microarray data, MCLR-treated larvae displayed behavioral alterations such as weakening response to the sudden darkness and hypoactivity in the dark. Our work reveals new molecular targets for MCLR and provides further insights into the molecular mechanisms of MCLR toxicity during early development. View Full-Text
Keywords: MCLR; zebrafish; gene expression; behavior; visual cycle MCLR; zebrafish; gene expression; behavior; visual cycle

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Tzima, E.; Serifi, I.; Tsikari, I.; Alzualde, A.; Leonardos, I.; Papamarcaki, T. Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure. Int. J. Mol. Sci. 2017, 18, 365.

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