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The Zebrafish Model in Animal and Human Health Research, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 September 2025 | Viewed by 9757

Special Issue Editors


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Guest Editor
1. Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90133 Palermo, Italy
2. Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90133 Palermo, Italy
Interests: anatomy; oxidative stress; molecular chaperones; cell signaling; cell biology; bioinformatics
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Special Issue Information

Dear Colleagues,

The zebrafish (Danio rerio) has become a widely used vertebrate model for biomedical and ecotoxicological research. Due to its high fertility rate, small size, rapid development and optical transparency during early development as well as its strong genetic similarity with humans, the zebrafish is particularly useful both to model human diseases and to address several questions about the effects of environmental contaminants on human development and health. Zebrafish are used as a model in all areas of environmental toxicology involving the study of the biological effects of toxic compounds in the natural environment, including their effects on humans and animals. Zebrafish are increasingly being employed in predictive toxicology, in the screening of contaminants and in the assessment of environmental matrices, permitting monitoring and, finally, allowing researchers to find adequate preventive strategies to protect life on planet Earth.  

In this Special Issue of the International Journal of Molecular Sciences, we focus our attention on the latest discoveries, methods and technology advancements as well as environmental toxicant assessments in zebrafish models which can provide knowledge which can be used to monitor and preserve animal and human health. We aim to provide a comprehensive update regarding the literature accessible to scientists within this field. Thus, we wish to invite investigators from basic, clinical and translational biomedical and ecotoxicological research or closely related disciplines to contribute with original articles, reviews, communications and concept papers.

Dr. Antonella Marino Gammazza
Dr. Marta Anna Szychlinska
Guest Editors

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Keywords

  • zebrafish
  • environmental toxicology
  • predictive toxicology

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Related Special Issue

Published Papers (7 papers)

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Research

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32 pages, 5488 KiB  
Article
Persistent Transcriptome Alterations in Zebrafish Embryos After Discontinued Opioid Exposure
by Ryan J. North, Gwendolyn Cooper, Lucas Mears, Brian Bothner, Mensur Dlakić and Christa S. Merzdorf
Int. J. Mol. Sci. 2025, 26(10), 4840; https://doi.org/10.3390/ijms26104840 - 19 May 2025
Viewed by 284
Abstract
Much attention has been paid to the public health crisis that has resulted from the opioid epidemic. Given the high number of opioid users that are of childbearing age, the impact of utero exposure is a serious concern. Unfortunately, there is little knowledge [...] Read more.
Much attention has been paid to the public health crisis that has resulted from the opioid epidemic. Given the high number of opioid users that are of childbearing age, the impact of utero exposure is a serious concern. Unfortunately, there is little knowledge regarding the consequences of opioid exposure during early development. While neurobehavioral effects of opioid exposure are well-documented, effects of exposure on embryogenesis remain largely unexplored. To address this gap in knowledge, we investigated the effects of oxycodone and fentanyl exposure on gene expression in zebrafish (Danio rerio) embryos using whole embryo RNA sequencing. Embryos were exposed to environmentally relevant (oxycodone HCl 10.6 ng/L and fentanyl citrate 0.629 ng/L) and therapeutically relevant doses (oxycodone HCl 35.14 μg/L and fentanyl citrate 3.14 μg/L) from 2 to 24 h post-fertilization (hpf), followed by another 24 h of opioid-free development. mRNA profiling at 48 hpf revealed dose- and drug-specific gene expression changes. Lower doses of oxycodone and fentanyl both induced more differentially expressed transcripts (DETs) than higher doses, potentially indicative of opioid receptor desensitization occurring at higher concentrations. In total, 892 DETs (corresponding to 866 genes) were identified across all conditions suggesting continued differential gene expression well after cessation of opioid exposure. Gene ontology analysis revealed changes in gene expression relating to extracellular matrix (ECM) organization, cell adhesion, and visual and nervous system formation. Key pathways include those involved in axon guidance, synapse formation, and ECM biosynthesis/remodeling, all of which have potential implications on neural connectivity and sensory development. These findings demonstrate that very early developmental exposure to opioids induces persistent transcriptomic changes which may have lasting implications for vertebrate cellular functions. Overall, these data provide insights into the molecular mechanisms of opioid-induced alterations during development. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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24 pages, 11888 KiB  
Article
Olfactory Dysfunction in a Novel Model of Prodromal Parkinson’s Disease in Adult Zebrafish
by Nathaniel W. Vorhees, Samantha L. Groenwold, Mackenzie T. Williams, Lexus S. Putt, Nereyda Sanchez-Gama, Grace A. Stalions, Gabriella M. Taylor, Heather E. Van Dort and Erika Calvo-Ochoa
Int. J. Mol. Sci. 2025, 26(10), 4474; https://doi.org/10.3390/ijms26104474 - 8 May 2025
Viewed by 403
Abstract
Olfactory dysfunction is a clinical marker of prodromal Parkinson’s disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates the olfactory impairment observed in prodromal PD without affecting motor function. We used zebrafish due [...] Read more.
Olfactory dysfunction is a clinical marker of prodromal Parkinson’s disease (PD), yet the underlying mechanisms remain unclear. To explore this relationship, we developed a zebrafish model that recapitulates the olfactory impairment observed in prodromal PD without affecting motor function. We used zebrafish due to their olfactory system’s similarity to mammals and their unique nervous system regenerative capacity. By injecting 6-hydroxydopamine (6-OHDA) into the dorsal telencephalic ventricle, we observed a significant loss of dopaminergic (DA) periglomerular neurons in the olfactory bulb (OB) and retrograde degeneration of olfactory sensory neurons (OSNs) in the olfactory epithelium (OE). These alterations impaired olfactory responses to cadaverine, an aversive odorant, while responses to alanine remained intact. 6-OHDA also triggered robust neuroinflammatory responses. By 7 days post-injection, dopaminergic synapses in the OB were remodeled, OSNs in the OE appeared recovered, and neuroinflammation subsided, leading to full recovery of olfactory responses to cadaverine. These findings highlight the remarkable neuroplasticity of zebrafish and suggest that this model of olfactory dysfunction associated with dopaminergic loss could provide valuable insights into some features of early PD pathology. Understanding the interplay between dopaminergic loss and olfactory dysfunction in a highly regenerative vertebrate may inform therapeutic strategies for individuals suffering from olfactory loss. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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17 pages, 4796 KiB  
Article
Vitamin E Mitigates Polystyrene-Nanoplastic-Induced Visual Dysfunction in Zebrafish Larvae
by Febriyansyah Saputra, Azzah Dyah Pramata, Agoes Soegianto and Shao-Yang Hu
Int. J. Mol. Sci. 2025, 26(3), 1216; https://doi.org/10.3390/ijms26031216 - 30 Jan 2025
Cited by 1 | Viewed by 1522
Abstract
Vitamin E (VitE), a potent antioxidant, has demonstrated significant potential in mitigating oxidative stress and cellular damage, making it a valuable agent for countering environmental toxicities, including those caused by polystyrene nanoplastics (PSNPs). This study examined the effects of PSNPs on the zebrafish [...] Read more.
Vitamin E (VitE), a potent antioxidant, has demonstrated significant potential in mitigating oxidative stress and cellular damage, making it a valuable agent for countering environmental toxicities, including those caused by polystyrene nanoplastics (PSNPs). This study examined the effects of PSNPs on the zebrafish visual system and evaluated the protective role of VitE. Zebrafish embryos were exposed to PSNPs (0.01, 0.1, 1, and 10 μg/mL) with or without 20 μM VitE co-treatment from fertilization to 6 days post-fertilization (dpf). Visual function, morphology, and molecular responses were assessed at 4 or 6 dpf. Exposure to PSNPs at concentrations of 0.1 to 10 μg/mL significantly increased bioaccumulation in the zebrafish eye in a concentration-dependent manner and disrupted the visual system. These disruptions caused a reduction in the eye-to-body length ratio and decreased optomotor response positivity and swimming distance, indicating impaired visual function and behavior. Furthermore, PSNPs elevated reactive oxygen species (ROS) levels, induced retinal apoptosis, and disrupted gene expression related to visual development (six6, pax2, pax6a, and pax6b), apoptosis (tp53, casp3, bax, and bcl2a), and antioxidant defense (sod1, cat, and gpx1a). VitE co-treatment significantly mitigated these adverse effects, reducing oxidative damage, restoring antioxidant defenses, and preserving retinal function. This study highlights the potential of VitE as a protective agent against PSNP-induced visual dysfunction and underlines the urgent need to address nanoplastic pollution to protect aquatic ecosystems. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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18 pages, 8240 KiB  
Article
Type 2 Diabetes Induces Mitochondrial Dysfunction in Zebrafish Skeletal Muscle Leading to Diabetic Myopathy via the miR-139-5p/NAMPT Pathway
by Zhanglin Chen, Zuoqiong Zhou, Qinhua Deng, Yunyi Zou, Bihan Wang, Shuaiwang Huang, Jiaqi Tian, Lan Zheng, Xiyang Peng and Changfa Tang
Int. J. Mol. Sci. 2025, 26(2), 752; https://doi.org/10.3390/ijms26020752 - 17 Jan 2025
Viewed by 1211
Abstract
Type 2 diabetes mellitus (T2DM) is a common metabolic disease that is frequently accompanied by multiple complications, including diabetic myopathy, a muscle disorder that is mainly manifested as decreased muscle function and reduced muscle mass. Diabetic myopathy is a relatively common complication among [...] Read more.
Type 2 diabetes mellitus (T2DM) is a common metabolic disease that is frequently accompanied by multiple complications, including diabetic myopathy, a muscle disorder that is mainly manifested as decreased muscle function and reduced muscle mass. Diabetic myopathy is a relatively common complication among patients with diabetes that is mainly attributed to mitochondrial dysfunction. Therefore, we investigated the mechanisms underlying diabetic myopathy development, focusing on the role of microRNAs (miRs). Zebrafish were fed a high-sugar diet for 8 weeks and immersed in a glucose solution to establish a model of T2DM. Notably, the fish exhibited impaired blood glucose homeostasis, increased lipid accumulation in the skeletal muscles, and decreased insulin levels in the skeletal muscle. Additionally, we observed various symptoms of diabetic myopathy, including a decreased cross-sectional area of skeletal muscle fibers, increased skeletal muscle fibrosis, a significant decline in exercise capacity, and a significant decrease in mitochondrial respiratory function. Mechanistically, bioinformatic analysis combined with various molecular analyses showed that the miR-139-5p/NAMPT pathway was involved in long-term high-glucose-induced mitochondrial dysfunction in the skeletal muscle, leading to diabetic myopathy. Conclusively, this study provides a basis for the development of novel strategies for the prevention and treatment of diabetic myopathy. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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15 pages, 4102 KiB  
Article
Abamectin Causes Neurotoxicity in Zebrafish Embryos
by Hongying Zhang, Yulong Liu, Yukun Huang, Kaiwen Zhao, Tingting Yu, Youjuan Wu, Zijia Yin, Meifeng Li, Dongming Li, Lihua Fan, Xiaowen Xu, Chengyu Hu and Shanghong Wang
Int. J. Mol. Sci. 2025, 26(1), 349; https://doi.org/10.3390/ijms26010349 - 3 Jan 2025
Viewed by 1069
Abstract
Abamectin is an insecticide, miticide and nematicide that has been extensively used in agriculture for many years. The excessive use of abamectin inevitably pollutes water and soil and might even cause adverse effects on aquatic biota. However, it is currently unclear how abamectin [...] Read more.
Abamectin is an insecticide, miticide and nematicide that has been extensively used in agriculture for many years. The excessive use of abamectin inevitably pollutes water and soil and might even cause adverse effects on aquatic biota. However, it is currently unclear how abamectin exposure causes neurotoxicity in aquatic organisms. Herein, the early neural system development was assessed in zebrafish embryos following abamectin exposure. After treatment with a concentration gradient of abamectin (0.055, 0.0825, 0.11 mg/L), the survival rate, average heart rate, pericardial edema area and yolk sac edema were all documented in zebrafish embryos (96 hpf). It was found that after abamectin exposure, embryonic brain development was impaired, and motor behaviors were also affected. The fluorescence intensity was reduced in the transgenic embryos (Eno2: GFP). The activities of acetylcholinesterase (AChE) and ATPase were decreased, and the expression of neurodevelopment-related genes, such as sox10, gap43, grin1b, abat, gad1b, grin2b, nestin and glsa, were all inhibited in zebrafish embryo treatment with abamectin. Furthermore, the reactive oxygen species (ROS) were triggered upon exposure to abamectin in zebrafish embryos along with the accumulation of ROS, eventually resulting in neuroapoptosis in the developing embryonic brain. In conclusion, neurodevelopmental toxicity was caused by oxidative stress-induced apoptosis in zebrafish embryos following abamectin exposure. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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Review

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21 pages, 1061 KiB  
Review
Emerging Frontiers in Zebrafish Embryonic and Adult-Derived Cell Lines
by Álvaro J. Arana, Laura González-Llera, Antón Barreiro-Iglesias and Laura Sánchez
Int. J. Mol. Sci. 2025, 26(9), 4351; https://doi.org/10.3390/ijms26094351 - 3 May 2025
Viewed by 535
Abstract
Zebrafish (Danio rerio) has become a pivotal vertebrate model in biomedical research, renowned for its genetic similarity to humans, optical transparency, rapid embryonic development, and amenability to experimental manipulation. In recent years, the derivation of cell lines from zebrafish embryos has [...] Read more.
Zebrafish (Danio rerio) has become a pivotal vertebrate model in biomedical research, renowned for its genetic similarity to humans, optical transparency, rapid embryonic development, and amenability to experimental manipulation. In recent years, the derivation of cell lines from zebrafish embryos has unlocked new possibilities for in vitro studies across developmental biology, toxicology, disease modeling, and genetic engineering. These embryo-derived cultures offer scalable, reproducible, and ethically favorable alternatives to in vivo approaches, enabling high-throughput screening and mechanistic exploration under defined conditions. This review provides a comprehensive overview of protocols for establishing and maintaining zebrafish embryonic cell lines, emphasizing culture conditions, pluripotency features, transfection strategies, and recent innovations such as genotype-defined mutant lines generated via CRISPR/Cas9 and feeder-free systems. We also highlight emerging applications in oncology, regenerative medicine, and functional genomics, positioning zebrafish cell lines as versatile platforms bridging animal models and next-generation in vitro systems. Its continued optimization holds promise for improved reproducibility, reduced animal use, and expanded translational impact in biomedical research. Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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23 pages, 1860 KiB  
Review
Zebrafish (Danio rerio) as a Model System to Investigate the Role of the Innate Immune Response in Human Infectious Diseases
by Maria Franza, Romualdo Varricchio, Giulia Alloisio, Giovanna De Simone, Stefano Di Bella, Paolo Ascenzi and Alessandra di Masi
Int. J. Mol. Sci. 2024, 25(22), 12008; https://doi.org/10.3390/ijms252212008 - 8 Nov 2024
Cited by 7 | Viewed by 3633
Abstract
The zebrafish (Danio rerio) has emerged as a valuable model for studying host-pathogen interactions due to its unique combination of characteristics. These include extensive sequence and functional conservation with the human genome, optical transparency in larvae that allows for high-resolution visualization [...] Read more.
The zebrafish (Danio rerio) has emerged as a valuable model for studying host-pathogen interactions due to its unique combination of characteristics. These include extensive sequence and functional conservation with the human genome, optical transparency in larvae that allows for high-resolution visualization of host cell-microbe interactions, a fully sequenced and annotated genome, advanced forward and reverse genetic tools, and suitability for chemical screening studies. Despite anatomical differences with humans, the zebrafish model has proven instrumental in investigating immune responses and human infectious diseases. Notably, zebrafish larvae rely exclusively on innate immune responses during the early stages of development, as the adaptive immune system becomes fully functional only after 4–6 weeks post-fertilization. This window provides a unique opportunity to isolate and examine infection and inflammation mechanisms driven by the innate immune response without the confounding effects of adaptive immunity. In this review, we highlight the strengths and limitations of using zebrafish as a powerful vertebrate model to study innate immune responses in infectious diseases. We will particularly focus on host-pathogen interactions in human infections caused by various bacteria (Clostridioides difficile, Staphylococcus aureus, and Pseudomonas aeruginosa), viruses (herpes simplex virus 1, SARS-CoV-2), and fungi (Aspergillus fumigatus and Candida albicans). Full article
(This article belongs to the Special Issue The Zebrafish Model in Animal and Human Health Research, 2nd Edition)
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