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Open AccessArticle

Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation

1
Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
2
Department of Central Laboratory, Mie University Hospital, Tsu, Mie 514-8507, Japan
3
Department of Genomic Medicine, Mie University Hospital, Tsu, Mie 514-8507, Japan
4
Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(4), 145; https://doi.org/10.3390/ph12040145
Received: 1 August 2019 / Revised: 19 September 2019 / Accepted: 22 September 2019 / Published: 24 September 2019
(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery)
The developing brain is extremely sensitive to many chemicals. Exposure to neurotoxicants during development has been implicated in various neuropsychiatric and neurological disorders, including autism spectrum disorders and schizophrenia. Various screening methods have been used to assess the developmental neurotoxicity (DNT) of chemicals, with most assays focusing on cell viability, apoptosis, proliferation, migration, neuronal differentiation, and neuronal network formation. However, assessment of toxicity during progenitor cell differentiation into neurons, astrocytes, and oligodendrocytes often requires immunohistochemistry, which is a reliable but labor-intensive and time-consuming assay. Here, we report the development of a triple-transgenic zebrafish line that expresses distinct fluorescent proteins in neurons (Cerulean), astrocytes (mCherry), and oligodendrocytes (mCitrine), which can be used to detect DNT during neuronal differentiation. Using in vivo fluorescence microscopy, we could detect DNT by 6 of the 10 neurotoxicants tested after exposure to zebrafish from 12 h to 5 days’ post-fertilization. Moreover, the chemicals could be clustered into three main DNT groups based on the fluorescence pattern: (i) inhibition of neuron and oligodendrocyte differentiation and stimulation of astrocyte differentiation; (ii) inhibition of neuron and oligodendrocyte differentiation; and (iii) inhibition of neuron and astrocyte differentiation, which suggests that reporter expression reflects the toxicodynamics of the chemicals. Thus, the triple-transgenic zebrafish line developed here may be a useful tool to assess DNT during neuronal differentiation. View Full-Text
Keywords: developmental neurotoxicity; neuronal differentiation; zebrafish; in vivo fluorescence imaging developmental neurotoxicity; neuronal differentiation; zebrafish; in vivo fluorescence imaging
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Koiwa, J.; Shiromizu, T.; Adachi, Y.; Ikejiri, M.; Nakatani, K.; Tanaka, T.; Nishimura, Y. Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation. Pharmaceuticals 2019, 12, 145.

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