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Zebrafish Models of Neurological Diseases and Disorders

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

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 17511

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Special Issue Editor

Prof. Dr. Jennifer L. Freeman

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Guest Editor

School of Health Sciences, Purdue University, 550 Stadium Mall Dr., HAMP-1163D, West Lafayette, IN 47907, USA
Interests: environmental and molecular toxicology; developmental origin of health and disease; genome and epigenome alterations; molecular cytogenetics; neurotoxicology; toxicogenomics; zebrafish model system
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Zebrafish (Danio rerio) present several strengths in biological research to fill the gap between in vitro and mammalian models. A substantial amount of research at multiple life stages and a completed reference genome enables research throughout the life span on genetic and epigenetic mechanisms of human disease including neurological diseases and disorders. Parallels in brain cellular structure, cellular signaling pathways, and neurodevelopmental processes occur for zebrafish and mammals. In addition, well-characterized neurobehavioral patterns in the zebrafish allows connection between genetic, epigenetic, phenotypic, and functional outcomes. Moreover, zebrafish are amenable to high-throughput screens and are being employed in drug discovery to identify novel neurotherapuetics. In fact, zebrafish models are now being used to study neuropathogenesis, to define molecular and epigenetic mechanisms, and in pharmaceutical screens for several human neurological diseases and disorders including neurodevelopmental disorders (e.g., Autism Spectrum Disorder), neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease), epilepsy, among others. This special issue will include a selection of original research papers and reviews highlighting the use of the zebrafish in studies of neurological diseases and disorders.

Prof. Dr. Jennifer L. Freeman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Alzheimer’s disease
Autism Spectrum Disorder
Behavior
CRISPR
Drug Discovery
Epilepsy
Epigenetics
Neurodegeneration
Neurodevelopment
Neurotoxicity
Non-mammalian models
Parkinson’s disease
Transgenic models
Zebrafish

Published Papers (3 papers)

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Research

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23 pages, 5133 KiB

Open AccessArticle

A Novel Function of the Lysophosphatidic Acid Receptor 3 (LPAR3) Gene in Zebrafish on Modulating Anxiety, Circadian Rhythm Locomotor Activity, and Short-Term Memory

by Yu-Nung Lin, Gilbert Audira, Nemi Malhotra, Nguyen Thi Ngoc Anh, Petrus Siregar, Jen-Her Lu, Hsinyu Lee and Chung-Der Hsiao

Int. J. Mol. Sci. 2020, 21(8), 2837; https://doi.org/10.3390/ijms21082837 - 18 Apr 2020

Cited by 6 | Viewed by 3510

Abstract

Lysophosphatidic acid (LPA) is a small lysophospholipid molecule that activates multiple cellular functions through pathways with G-protein-coupled receptors. So far, six LPA receptors (LPAR1 to LPAR6) have been discovered and each one of them can connect to the downstream cell message-transmitting network. A previous study demonstrated that LPA receptors found in blood-producing stem cells can enhance erythropoietic processes through the activation of LPAR3. In the current study, newly discovered functions of LPAR3 were identified through extensive behavioral tests in lpar3 knockout (KO) zebrafish. It was found that the adult lpar3 KO zebrafish display an abnormal movement orientation and altered exploratory behavior compared to that of the control group in the three-dimensional locomotor and novel tank tests, respectively. Furthermore, consistent with those results, in the circadian rhythm locomotor activity test, the lpar3 KO zebrafish showed a lower level of angular velocity and average speed during the light cycles, indicating an hyperactivity-like behavior. In addition, the mutant fish also exhibited considerably higher locomotor activity during the dark cycle. Supporting those findings, this phenomenon was also displayed in the lpar3 KO zebrafish larvae. Furthermore, several important behavior alterations were also observed in the adult lpar3 KO fish, including a lower degree of aggression, less interest in conspecific social interaction, and looser shoal formation. However, there was no significant difference regarding the predator avoidance behavior between the mutant and the control fish. In addition, lpar3 KO zebrafish displayed memory deficiency in the passive avoidance test. These in vivo results support for the first time that the lpar3 gene plays a novel role in modulating behaviors of anxiety, aggression, social interaction, circadian rhythm locomotor activity, and memory retention in zebrafish. Full article

(This article belongs to the Special Issue Zebrafish Models of Neurological Diseases and Disorders)

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12 pages, 3041 KiB

Open AccessArticle

Development of a Modified Three-Day T-maze Protocol for Evaluating Learning and Memory Capacity of Adult Zebrafish

by Bui Thi Ngoc Hieu, Nguyen Thi Ngoc Anh, Gilbert Audira, Stevhen Juniardi, Rhenz Alfred D. Liman, Oliver B. Villaflores, Yu-Heng Lai, Jung-Ren Chen, Sung-Tzu Liang, Jong-Chin Huang and Chung-Der Hsiao

Int. J. Mol. Sci. 2020, 21(4), 1464; https://doi.org/10.3390/ijms21041464 - 21 Feb 2020

Cited by 23 | Viewed by 6908

Abstract

A T-maze test is an experimental approach that is used in congenital research. However, the food reward-based protocol for the T-maze test in fish has low efficiency and a long training period. The aim of this study is to facilitate the T-maze conditions by using a combination of the principles of passive avoidance and a spatial memory test. In our modified T-maze settings, electric shock punishment (1–2 V, 0.3–0.5 mA) is given at the left arm, with a green cue at the right arm. Also, the depth of both arms of the T-maze was increased. The parameters measured in our T-maze design were latency, freezing time, and time spent in different areas of the T-maze. We validated the utility of our modified T-maze protocol by showing the consistent finding of memory impairment in ZnCl₂−treated fish, which has been previously detected with the passive avoidance test. In addition, we also tested the spatial memory performance of leptin a (lepa) mutants which displayed an obesity phenotype. The results showed that although the learning and memory performance for lepa KO fish were similar to control fish, they displayed a higher freezing behavior during the training phase. In conclusion, we have established a modified T-maze protocol that can be used to evaluate the anxiety, learning, and memory capacity of adult zebrafish within three days, for the first time. Full article

(This article belongs to the Special Issue Zebrafish Models of Neurological Diseases and Disorders)

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Review

Jump to: Research

14 pages, 720 KiB

Open AccessReview

Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration

by Ola Wasel and Jennifer L. Freeman

Int. J. Mol. Sci. 2020, 21(17), 5981; https://doi.org/10.3390/ijms21175981 - 20 Aug 2020

Cited by 27 | Viewed by 6504

Abstract

The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson’s disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish’s dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson’s disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson’s disease associated with the dopaminergic system. Full article

(This article belongs to the Special Issue Zebrafish Models of Neurological Diseases and Disorders)

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