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

2020 ◽  
Vol 21 (17) ◽  
pp. 5981
Author(s):  
Ola Wasel ◽  
Jennifer L. Freeman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Dopaminergic System ◽  
Neuronal Loss ◽  
Dopaminergic Neurodegeneration ◽  
Biological Studies ◽  
Vertebrate Model ◽  
Dopaminergic Neuronal Loss ◽  
6 Hydroxydopamine

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.

scholarly journals Peripheral Inflammation Increases the Damage in Animal Models of Nigrostriatal Dopaminergic Neurodegeneration: Possible Implication in Parkinson's Disease Incidence

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
A. Machado ◽  
A. J. Herrera ◽  
J. L. Venero ◽  
M. Santiago ◽  
R. M. De Pablos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Substantia Nigra ◽  
Dopaminergic System ◽  
Disease Incidence ◽  
Epidemiological Studies ◽  
Peripheral Inflammation ◽  
Dopaminergic Neurodegeneration ◽  
6 Hydroxydopamine

Inflammatory processes described in Parkinson’s disease (PD) and its animal models appear to be important in the progression of the pathogenesis, or even a triggering factor. Here we review that peripheral inflammation enhances the degeneration of the nigrostriatal dopaminergic system induced by different insults; different peripheral inflammations have been used, such as IL-1β and the ulcerative colitis model, as well as insults to the dopaminergic system such as 6-hydroxydopamine or lipopolysaccharide. In all cases, an increased loss of dopaminergic neurons was described; inflammation in the substantia nigra increased, displaying a great activation of microglia along with an increase in the production of cytokines such as IL-1β and TNF-α. Increased permeability or disruption of the BBB, with overexpression of the ICAM-1 adhesion molecule and infiltration of circulating monocytes into the substantia nigra, is also involved, since the depletion of circulating monocytes prevents the effects of peripheral inflammation. Data are reviewed in relation to epidemiological studies of PD.

Dopaminergic neuronal loss in transgenic mice expressing the Parkinson's disease-associated UCH-L1 I93M mutant

2007 ◽  
Vol 50 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Rieko Setsuie ◽  
Yu-Lai Wang ◽  
Hideki Mochizuki ◽  
Hitoshi Osaka ◽  
Hideki Hayakawa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mice ◽  
Neuronal Loss ◽  
Dopaminergic Neuronal Loss

scholarly journals MMP-3 Contributes to Nigrostriatal Dopaminergic Neuronal Loss, BBB Damage, and Neuroinflammation in an MPTP Mouse Model of Parkinson’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Young Cheul Chung ◽  
Yoon-Seong Kim ◽  
Eugene Bok ◽  
Tae Young Yune ◽  
Sungho Maeng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Nigrostriatal Pathway ◽  
Matrix Metalloproteinase 3 ◽  
Genetic Ablation ◽  
Dopaminergic Neuronal Loss ◽  
Peripheral Immune Cells

The present study examined whether matrix metalloproteinase-3 (MMP-3) participates in the loss of dopaminergic (DA) neurons in the nigrostriatal pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease with blood brain barrier (BBB) damage and infiltration of peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain sections from MPTP-treated mice showed that MPTP induced significant degeneration of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and immunostaining revealed that MPTP caused damage to the BBB and increased the number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN). Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved motor function. This neuroprotective effect afforded by MMP-3 deletion was associated with the suppression of BBB disruption and a decrease in the number of ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3 could play a crucial role in neurodegenerative diseases such as PD in which BBB damage and neuroinflammation are implicated.

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