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

The zebrafish (<i>Danio rerio</i>) 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 hi...

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Main Authors: Ola Wasel, Jennifer L. Freeman
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/17/5981
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author Ola Wasel
Jennifer L. Freeman
author_facet Ola Wasel
Jennifer L. Freeman
author_sort Ola Wasel
collection DOAJ
description The zebrafish (<i>Danio rerio</i>) 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 <i>dj1</i>, <i>pink1</i>, and <i>prkn</i> 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.
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spelling doaj.art-a51bb4bd78324376b58baa30c6eafc812023-11-20T10:43:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117598110.3390/ijms21175981Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic NeurodegenerationOla Wasel0Jennifer L. Freeman1School of Health Sciences, Purdue University, West Lafayette, IN 47907, USASchool of Health Sciences, Purdue University, West Lafayette, IN 47907, USAThe zebrafish (<i>Danio rerio</i>) 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 <i>dj1</i>, <i>pink1</i>, and <i>prkn</i> 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.https://www.mdpi.com/1422-0067/21/17/5981dj1dopamineMPTPneurotransmissionparaquatParkinson’s disease
spellingShingle Ola Wasel
Jennifer L. Freeman
Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
International Journal of Molecular Sciences
dj1
dopamine
MPTP
neurotransmission
paraquat
Parkinson’s disease
title Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
title_full Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
title_fullStr Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
title_full_unstemmed Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
title_short Chemical and Genetic Zebrafish Models to Define Mechanisms of and Treatments for Dopaminergic Neurodegeneration
title_sort chemical and genetic zebrafish models to define mechanisms of and treatments for dopaminergic neurodegeneration
topic dj1
dopamine
MPTP
neurotransmission
paraquat
Parkinson’s disease
url https://www.mdpi.com/1422-0067/21/17/5981
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