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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 11444

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Prof. Dr. Pierre-Olivier Angrand

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Guest Editor

Université de Lille, CNRS, INSERM, CHU Lille, Centre Oscar Lambret, UMR 9020–UMR 1277–Canther–Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France
Interests: epigenetics; zebrafish model; cancer
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Dear Colleagues,

In the 1950s, the zebrafish emerged as a model for studying early development but was rapidly used in broader research fields. The success of the zebrafish in research is mainly due to the attributes that make it an exceptional experimental model. Notably, zebrafish are robust and easy to maintain at low husbandry costs. Zebrafish have a high fecundity rate, producing around 100–200 embryos per clutch and per week, making statistical analyses robust. Zebrafish embryos develop externally and are optically clear, providing a remarkable platform for microscopic observations of early development. The zebrafish genome is fully sequenced, and a comparison to the human reference genome revealed that about 84% of genes involved in human diseases have a zebrafish orthologue. Thousands of zebrafish mutants coming from large-scale mutagenesis screens are available. Additionally, a variety of genetic engineering approaches, such as transgenesis, morpholino-mediated gene expression knockdown, or genome-editing technologies, can be applied to the zebrafish model to question the function of genes. Over the last two decades, the zebrafish has continued to increase in popularity, becoming increasingly used to investigate human disease mechanisms, to model human pathologies, and for drug discovery. At present, the zebrafish model is largely applied to the biomedical field in order to study a wide range of human diseases including developmental syndromes, metabolic defects, neurological and behavioral disorders, cancer, and host–microbe interactions.

The goal of this Special Issue is to present the current knowledge on the use of the zebrafish model in biomedical research in order to decipher the molecular mechanisms responsible for human diseases and to set up rational strategies for drug discovery.

The formats for submissions include original research reports, reviews, perspectives/opinions, and methodology articles.

Prof. Dr. Pierre-Olivier Angrand
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

zebrafish
cancer
metabolic diseases
neurological disorders
infectious diseases
xenografts
drug discovery

Published Papers (6 papers)

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Research

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16 pages, 3737 KiB

Open AccessArticle

Deletion of the chd7 Hinders Oligodendrocyte Progenitor Cell Development and Myelination in Zebrafish

by Lingyu Shi, Zongyi Wang, Yujiao Li, Zheng Song, Wu Yin and Bing Hu

Int. J. Mol. Sci. 2023, 24(17), 13535; https://doi.org/10.3390/ijms241713535 - 31 Aug 2023

Viewed by 1217

Abstract

CHD7, an encoding ATP-dependent chromodomain helicase DNA-binding protein 7, has been identified as the causative gene involved in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia choanae, Retardation of growth and/or development, Genital abnormalities and Ear abnormalities). Although studies in rodent models have expanded our understanding of CHD7, its role in oligodendrocyte (OL) differentiation and myelination in zebrafish is still unclear. In this study, we generated a chd7-knockout strain with CRISPR/Cas9 in zebrafish. We observed that knockout (KO) of chd7 intensely impeded the oligodendrocyte progenitor cells’ (OPCs) migration and myelin formation due to massive expression of chd7 in oilg2⁺ cells, which might provoke upregulation of the MAPK signal pathway. Thus, our study demonstrates that chd7 is critical to oligodendrocyte migration and myelination during early development in zebrafish and describes a mechanism potentially associated with CHARGE syndrome. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Biomedical Studies)

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14 pages, 3716 KiB

Open AccessArticle

Obesity Impairs Cognitive Function with No Effects on Anxiety-like Behaviour in Zebrafish

by Alejandra Godino-Gimeno, Per-Ove Thörnqvist, Mauro Chivite, Jesús M. Míguez, Svante Winberg and José Miguel Cerdá-Reverter

Int. J. Mol. Sci. 2023, 24(15), 12316; https://doi.org/10.3390/ijms241512316 - 01 Aug 2023

Viewed by 2091

Abstract

Over the last decade, the zebrafish has emerged as an important model organism for behavioural studies and neurological disorders, as well as for the study of metabolic diseases. This makes zebrafish an alternative model for studying the effects of energy disruption and nutritional quality on a wide range of behavioural aspects. Here, we used the zebrafish model to study how obesity induced by overfeeding regulates emotional and cognitive processes. Two groups of fish (n = 24 per group) were fed at 2% (CTRL) and 8% (overfeeding-induced obesity, OIO) for 8 weeks and tested for anxiety-like behaviour using the novel tank diving test (NTDT). Fish were first tested using a short-term memory test (STM) and then trained for four days for a long-term memory test (LTM). At the end of the experiment, fish were euthanised for biometric sampling, total lipid content, and triglyceride analysis. In addition, brains (eight per treatment) were dissected for HPLC determination of monoamines. Overfeeding induced faster growth and obesity, as indicated by increased total lipid content. OIO had no effect on anxiety-like behaviour. Animals were then tested for cognitive function (learning and memory) using the aversive learning test in Zantiks AD units. Results show that both OIO and CTRL animals were able to associate the aversive stimulus with the conditioned stimulus (conditioned learning), but OIO impaired STM regardless of fish sex, revealing the effects of obesity on cognitive processes in zebrafish. Obese fish did not show a deficiency in monoaminergic transmission, as revealed by quantification of total brain levels of dopamine and serotonin and their metabolites. This provides a reliable protocol for assessing the effect of metabolic disease on cognitive and behavioural function, supporting zebrafish as a model for behavioural and cognitive neuroscience. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Biomedical Studies)

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12 pages, 1504 KiB

Open AccessArticle

Nicotine and Cytisine Embryotoxicity in the Experimental Zebrafish Model

by Wojciech Świątkowski, Barbara Budzyńska, Monika Maciąg, Agnieszka Świątkowska, Przemko Tylżanowski, Mansur Rahnama-Hezavah, Piotr Stachurski and Renata Chałas

Int. J. Mol. Sci. 2023, 24(15), 12094; https://doi.org/10.3390/ijms241512094 - 28 Jul 2023

Cited by 2 | Viewed by 1561

Abstract

Tobacco smoking is one of the most serious health problems. Potentially lethal effects of nicotine for adults can occur with as little as 30 to 60 mg, although severe symptoms can arise with lower doses. Furthermore, the route of administration also influences the toxicity. Cytisine is one of the most popular medications in nicotinism treatment. Like nicotine, cytisine is a plant alkaloid, signaling through nicotinic acetylcholine receptors. Our study evaluated the effects of cytisine in nicotine-induced embryotoxic effects using zebrafish larvae. We examined the teratogenicity of nicotine and cytisine alone or in combination. Nicotine increased mortality and delayed hatching of zebrafish larvae in a dose-dependent manner. Cytisine did not affect mortality in a wide range of concentrations, and hatching delay was observed only at the highest concentrations, above 2 mM. Administering compounds together partially reduced the adverse teratogenic effect induced by nicotine alone. The protective effect of cytisine against the nicotine effect, observed in zebrafish, will contribute to future studies or treatments related to nicotine addiction or prenatal nicotine exposure in humans. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Biomedical Studies)

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11 pages, 2394 KiB

Open AccessArticle

Behavioral Study of 3- and 5-Halocytisine Derivatives in Zebrafish Using the Novel Tank Diving Test (NTT)

by Amaury Farías-Cea, Cristóbal Leal, Martín Hödar-Salazar, Erica Esparza, Luis Martínez-Duran, Irma Fuentes and Patricio Iturriaga-Vásquez

Int. J. Mol. Sci. 2023, 24(13), 10635; https://doi.org/10.3390/ijms241310635 - 25 Jun 2023

Cited by 3 | Viewed by 1612

Abstract

Anxiety is a serious mental disorder, and recent statistics have determined that 35.12% of the global population had an anxiety disorder during the COVID-19 pandemic. A mechanism associated with anxiolytic effects is related to nicotinic acetylcholine receptor (nAChR) agonists, principally acting on the α4β2 nAChR subtype. nAChRs are present in different animal models, including murine and teleosteos ones. Zebrafish has become an ideal animal model due to its high human genetic similarities (70%), giving it high versatility in different areas of study, among them in behavioral studies related to anxiety. The novel tank diving test (NTT) is one of the many paradigms used for studies on new drugs related to their anxiolytic effect. In this work, an adult zebrafish was used to determine the behavioral effects of 3- and 5-halocytisine derivatives, using the NTT at different doses. Our results show that substitution at position 3 by chlorine or bromine decreases the time spent by the fish at the bottom compared to the control. However, the 3-chloro derivative at higher doses increases the bottom dwelling time. In contrast, substitution at the 5 position increases bottom dwelling at all concentrations showing no anxiolytic effects in this model. Unexpected results were observed with the 5-chlorocytisine derivative, which at a concentration of 10 mg/L produced a significant decrease in bottom dwelling and showed high times of freezing. In conclusion, the 3-chloro and 3-bromo derivatives show an anxiolytic effect, the 3-chlorocytisine derivative being more potent than the 3-bromo derivative, with the lowest time at the bottom of the tank at 1mg/L. On the other hand, chlorine, and bromine at position 5 produce an opposite effect. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Biomedical Studies)

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Review

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14 pages, 289 KiB

Open AccessReview

Non-Genetic-Induced Zebrafish Model for Type 2 Diabetes with Emphasis on Tools in Model Validation

by Olakunle Sanni, Thandi Fasemore and Pilani Nkomozepi

Int. J. Mol. Sci. 2024, 25(1), 240; https://doi.org/10.3390/ijms25010240 - 23 Dec 2023

Viewed by 796

Abstract

The unrelenting increase in the incidence of type 2 diabetes (T2D) necessitates the urgent need for effective animal models to mimic its pathophysiology. Zebrafish possess human-like metabolic traits and share significant genetic similarities, making them valuable candidates for studying metabolic disorders, including T2D. This review emphasizes the critical role of animal models in diabetes research, especially focusing on zebrafish as an alternative model organism. Different approaches to a non-genetic model of T2D in zebrafish, such as the glucose solution, diet-induced, chemical-induced, and combined diet-induced and glucose solution methods, with an emphasis on model validation using indicators of T2D, were highlighted. However, a significant drawback lies in the validation of these models. Some of these models have not extensively demonstrated persistent hyperglycemia or response to insulin resistance and glucose tolerance tests, depicted the morphology of the pancreatic β-cell, or showed their response to antidiabetic drugs. These tools are crucial in T2D pathology. Future research on non-genetic models of T2D in zebrafish must extensively focus on validating the metabolic deficits existing in the model with the same metabolic defects in humans and improve on the existing models for a better understanding of the molecular mechanisms underlying T2D and exploring potential therapeutic interventions. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Biomedical Studies)

14 pages, 2114 KiB

Open AccessReview

The Zebrafish Embryo as a Model Organism for Testing mRNA-Based Therapeutics

by Tjessa Bondue, Sante Princiero Berlingerio, Lambertus van den Heuvel and Elena Levtchenko

Int. J. Mol. Sci. 2023, 24(13), 11224; https://doi.org/10.3390/ijms241311224 - 07 Jul 2023

Cited by 5 | Viewed by 3111

Abstract

mRNA-based therapeutics have revolutionized the world of molecular therapy and have proven their potential in the vaccination campaigns for SARS-CoV2 and clinical trials for hereditary disorders. Preclinical studies have mainly focused on in vitro and rodent studies. However, research in rodents is costly and labour intensive, and requires ethical approval for all interventions. Zebrafish embryonic disease models are not always classified as laboratory animals and have been shown to be extremely valuable for high-throughput drug testing. Zebrafish larvae are characterized by their small size, optical transparency and high number of embryos, and are therefore also suited for the study of mRNA-based therapeutics. First, the one-cell stage injection of naked mRNA can be used to assess the effectivity of gene addition in vivo. Second, the intravascular injection in older larvae can be used to assess tissue targeting efficiency of (packaged) mRNA. In this review, we describe how zebrafish can be used as a steppingstone prior to testing mRNA in rodent models. We define the procedures that can be employed for both the one-cell stage and later-stage injections, as well as the appropriate procedures for post-injection follow-up. Full article

(This article belongs to the Special Issue Zebrafish as a Model for Biomedical Studies)

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