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Toxin-Based Rodent Models of Parkinson’s Disease

Cenci, M. Angela LU and Sgambato, Véronique (2021) In Neuromethods 160. p.3-19
Abstract

A major pathological hallmark of Parkinson’s disease (PD) is a severe degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNc) projecting to the motor part of the striatum. Therefore, there is a long-standing interest in using animal models with severe nigrostriatal degeneration for experimental research. Pathophysiological and behavioral features of PD are best studied in mammalian species endowed with well-developed corticobasal ganglia thalamocortical loops, such as rodents. Different toxins can be used to generate nigrostriatal damage, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat, and rotenone. Models based on 6-OHDA lesions provide the main... (More)

A major pathological hallmark of Parkinson’s disease (PD) is a severe degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNc) projecting to the motor part of the striatum. Therefore, there is a long-standing interest in using animal models with severe nigrostriatal degeneration for experimental research. Pathophysiological and behavioral features of PD are best studied in mammalian species endowed with well-developed corticobasal ganglia thalamocortical loops, such as rodents. Different toxins can be used to generate nigrostriatal damage, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat, and rotenone. Models based on 6-OHDA lesions provide the main advantage of a severe and reproducible DA lesions. Models based on MPTP provide easy and versatile tools to rapidly evaluate potential neuroprotective treatments. Models based on paraquat and rotenone are appealing for their relevance to some well-known environmental risk factors of the human PD, although they yield only partial dopaminergic degeneration and entail a considerable risk of nonspecific toxicity. The main general limitation of neurotoxin-based models is that they do not replicate some characterizing features of PD pathology, such as the formation of Lewy body–like proteinaceous aggregates or the anatomical pattern of neurodegeneration, which also affects nondopaminergic brain regions.

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author
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organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 6-Hydroxydopamine, Animal models, Paraquat, Parkinson’s disease, Rodents, Rotenone, Toxin
host publication
Neuromethods
series title
Neuromethods
volume
160
pages
17 pages
publisher
Humana Press
external identifiers
  • scopus:85090247231
ISSN
0893-2336
1940-6045
ISBN
978-1-0716-0911-8
978-1-0716-0912-5
DOI
10.1007/978-1-0716-0912-5_1
language
English
LU publication?
yes
id
3695f143-2817-447a-85d8-94b750bcfd8f
date added to LUP
2020-09-14 11:34:58
date last changed
2020-09-23 08:15:07
@inbook{3695f143-2817-447a-85d8-94b750bcfd8f,
  abstract     = {<p>A major pathological hallmark of Parkinson’s disease (PD) is a severe degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNc) projecting to the motor part of the striatum. Therefore, there is a long-standing interest in using animal models with severe nigrostriatal degeneration for experimental research. Pathophysiological and behavioral features of PD are best studied in mammalian species endowed with well-developed corticobasal ganglia thalamocortical loops, such as rodents. Different toxins can be used to generate nigrostriatal damage, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat, and rotenone. Models based on 6-OHDA lesions provide the main advantage of a severe and reproducible DA lesions. Models based on MPTP provide easy and versatile tools to rapidly evaluate potential neuroprotective treatments. Models based on paraquat and rotenone are appealing for their relevance to some well-known environmental risk factors of the human PD, although they yield only partial dopaminergic degeneration and entail a considerable risk of nonspecific toxicity. The main general limitation of neurotoxin-based models is that they do not replicate some characterizing features of PD pathology, such as the formation of Lewy body–like proteinaceous aggregates or the anatomical pattern of neurodegeneration, which also affects nondopaminergic brain regions.</p>},
  author       = {Cenci, M. Angela and Sgambato, Véronique},
  booktitle    = {Neuromethods},
  isbn         = {978-1-0716-0911-8},
  issn         = {0893-2336},
  language     = {eng},
  pages        = {3--19},
  publisher    = {Humana Press},
  series       = {Neuromethods},
  title        = {Toxin-Based Rodent Models of Parkinson’s Disease},
  url          = {http://dx.doi.org/10.1007/978-1-0716-0912-5_1},
  doi          = {10.1007/978-1-0716-0912-5_1},
  volume       = {160},
  year         = {2021},
}