Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation
| Autor: | Kaname Nakatani, Takashi Shiromizu, Toshio Tanaka, Makoto Ikejiri, Yuhei Nishimura, Yuka Adachi, Junko Koiwa |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
in vivo fluorescence imaging
Pharmaceutical Science lcsh:Medicine lcsh:RS1-441 Article lcsh:Pharmacy and materia medica Astrocyte differentiation Drug Discovery medicine Biological neural network Viability assay Progenitor cell Zebrafish neuronal differentiation biology lcsh:R Oligodendrocyte differentiation biology.organism_classification zebrafish Cell biology medicine.anatomical_structure nervous system Molecular Medicine developmental neurotoxicity Neuron mCherry |
| Zdroj: | Pharmaceuticals, Vol 12, Iss 4, p 145 (2019) Pharmaceuticals Volume 12 Issue 4 |
| ISSN: | 1424-8247 |
| Popis: | 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&rsquo 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. |
| Databáze: | OpenAIRE |
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