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Zebrafish Models of Neurological Diseases and Disorders
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Zebrafish Models of Neurological Diseases and Disorders

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 20462

Special Issue Editor

Dr. Jennifer L. Freeman

E-Mail Website
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

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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

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Published Papers (3 papers)

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Research

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23 pages, 5133 KiB  
Article
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 9 | Viewed by 4204
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 [...] Read more.
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  
Article
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 32 | Viewed by 8048
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 [...] Read more.
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

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14 pages, 720 KiB  
Review
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 35 | Viewed by 7517
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 [...] Read more.
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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