Inorganic arsenic alters the development of dopaminergic neurons but not serotonergic neurons and induces motor neuron development via Sonic hedgehog pathway in zebrafish

Kanungo, Jyotshna; Twaddle, Nathan C.; Silva, Camila; Robinson, Bonnie; Wolle, Mesay Mulugeta; Conklin, Sean D.; MacMahon, Shaun; Gu, Qiang; Edhlund, Ian; Benjamin, Linda; Beland, Frederick A.; Fitzpatrick, Suzanne

doi:10.1016/j.neulet.2022.137042

Cited by 5 publications

(14 citation statements)

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“…It is interesting to note that there was no alteration in six genes of the Hedgehog signaling pathway including ptch1, a receptor of the ligand Shh (Tukachinsky et al, 2016), because in our previous study, we showed that in sodium arsenitetreated hb9-GFP transgenic larvae, Shh signaling was involved in supernumerary spinal motor neuron generation (Kanungo et al, 2023). Because its receptor expression did not change (current study), the data indicate that the level of Shh possibly changed, which our earlier study suggested (Kanungo et al, 2023). Arsenic is indicated as a major contributor to autism spectrum disorder development (Baj et al, 2021).…”

Section: Discussionmentioning

confidence: 92%

“…: 4091‐99‐0; purity ≥97%) were purchased from Sigma‐Aldrich (St. Louis, MO, USA). The identity and purity of sodium arsenite was confirmed by inductively coupled plasma mass spectrometry (Kanungo et al, 2023). All other reagents were purchased from Sigma‐Aldrich unless otherwise indicated.…”

Section: Methodsmentioning

confidence: 99%

“…Wild‐type zebrafish embryos/larvae were used for this study. For treatment with sodium arsenite (200 mg/L), 5 h postfertilization (hpf) embryos were used (Kanungo et al, 2023). This concentration was chosen based on our previous study, which showed that there were alterations in acetylcholinesterase activity as well as motor neuron and dopaminergic neuron development (Kanungo et al, 2023).…”

Section: Methodsmentioning

confidence: 99%

“…Zebrafish embryos and larvae are ideal alternative model systems to study chemically induced toxicities (Kanungo et al, 2014). We have shown that inorganic arsenic alters the development of dopaminergic neurons but not serotonergic neurons in zebrafish larvae (Kanungo et al, 2023). We also showed that arsenic induced supernumerary motor neuron development via activation of the Sonic hedgehog (Shh) pathway (Kanungo et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

“…We have shown that inorganic arsenic alters the development of dopaminergic neurons but not serotonergic neurons in zebrafish larvae (Kanungo et al, 2023). We also showed that arsenic induced supernumerary motor neuron development via activation of the Sonic hedgehog (Shh) pathway (Kanungo et al, 2023). Inorganic arsenic modulates several signaling pathways (Chen & Costa, 2018; Laine & Fry, 2018; Nail et al, 2022; Phillips et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Gene expression analyses reveal potential mechanism of inorganic arsenic‐induced apoptosis in zebrafish

Silva,

Kudlyk,

Tryndyak

et al. 2023

J of Applied Toxicology

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Our previous study showed that sodium arsenite (200 mg/L) affected the nervous system and induced motor neuron development via the Sonic hedgehog pathway in zebrafish larvae. To gain more insight into the effects of arsenite on other signaling pathways, including apoptosis, we have performed quantitative polymerase chain reaction array‐based gene expression analyses. The 96‐well array plates contained primers for 84 genes representing 10 signaling pathways that regulate several biological functions, including apoptosis. We exposed eggs at 5 h postfertilization until the 72 h postfertilization larval stage to 200 mg/L sodium arsenite. In the Janus kinase/signal transducers and activators of transcription, nuclear factor κ‐light‐chain‐enhancer of activated B cells, and Wingless/Int‐1 signaling pathways, the expression of only one gene in each pathway was significantly altered. The expression of multiple genes was altered in the p53 and oxidative stress pathways. Sodium arsenite induced excessive apoptosis in the larvae. This compelled us to analyze specific genes in the p53 pathway, including cdkn1a, gadd45aa, and gadd45ba. Our data suggest that the p53 pathway is likely responsible for sodium arsenite‐induced apoptosis. In addition, sodium arsenite significantly reduced global DNA methylation in the zebrafish larvae, which may indicate that epigenetic factors could be dysregulated after arsenic exposure. Together, these data elucidate potential mechanisms of arsenic toxicity that could improve understanding of arsenic's effects on human health.

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Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Gene expression analyses reveal potential mechanism of inorganic arsenic‐induced apoptosis in zebrafish

Silva,

Kudlyk,

Tryndyak

et al. 2023

J of Applied Toxicology

Self Cite

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The uses of zebrafish (Danio rerio) as an in vivo model for toxicological studies: A review based on bibliometrics

Zhao,

Chen,

et al. 2024

Ecotoxicology and Environmental Safety

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Embryonic Zebrafish as a Model for Investigating the Interaction between Environmental Pollutants and Neurodegenerative Disorders

Yin,

Horzmann

2024

Biomedicines

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Environmental pollutants have been linked to neurotoxicity and are proposed to contribute to neurodegenerative disorders. The zebrafish model provides a high-throughput platform for large-scale chemical screening and toxicity assessment and is widely accepted as an important animal model for the investigation of neurodegenerative disorders. Although recent studies explore the roles of environmental pollutants in neurodegenerative disorders in zebrafish models, current knowledge of the mechanisms of environmentally induced neurodegenerative disorders is relatively complex and overlapping. This review primarily discusses utilizing embryonic zebrafish as the model to investigate environmental pollutants-related neurodegenerative disease. We also review current applicable approaches and important biomarkers to unravel the underlying mechanism of environmentally related neurodegenerative disorders. We found embryonic zebrafish to be a powerful tool that provides a platform for evaluating neurotoxicity triggered by environmentally relevant concentrations of neurotoxic compounds. Additionally, using variable approaches to assess neurotoxicity in the embryonic zebrafish allows researchers to have insights into the complex interaction between environmental pollutants and neurodegenerative disorders and, ultimately, an understanding of the underlying mechanisms related to environmental toxicants.

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Inorganic arsenic alters the development of dopaminergic neurons but not serotonergic neurons and induces motor neuron development via Sonic hedgehog pathway in zebrafish

Cited by 5 publications

References 54 publications

Gene expression analyses reveal potential mechanism of inorganic arsenic‐induced apoptosis in zebrafish

Gene expression analyses reveal potential mechanism of inorganic arsenic‐induced apoptosis in zebrafish

The uses of zebrafish (Danio rerio) as an in vivo model for toxicological studies: A review based on bibliometrics

Embryonic Zebrafish as a Model for Investigating the Interaction between Environmental Pollutants and Neurodegenerative Disorders

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