当前位置： SCI文献检索 > NEUROSCIENCE期刊下所有文献 > Development and characterisation of a novel rat model of Parkinson's disease induced by sequential intranigral administration of AAV-α-synuclein and the pesticide, rotenone.

Development and characterisation of a novel rat model of Parkinson's disease induced by sequential intranigral administration of AAV-α-synuclein and the pesticide, rotenone.

Abstract：

:Modeling Parkinson's disease remains a major challenge for preclinical researchers, as existing models fail to reliably recapitulate all of the classic features of the disease, namely, the progressive emergence of a bradykinetic motor syndrome with underlying nigrostriatal α-synuclein protein accumulation and nigrostriatal neurodegeneration. One limitation of the existing models is that they are normally induced by a single neuropathological insult, whereas the human disease is thought to be multifactorial with genetic and environmental factors contributing to the disease pathogenesis. Thus, in order to develop a more relevant model, we sought to determine if administration of the Parkinson's disease-associated pesticide, rotenone, into the substantia nigra of rats overexpressing the Parkinson's disease-associated protein, α-synuclein, could reliably model the triad of classic features of the human disease. To do so, rats underwent stereotaxic surgery for unilateral delivery of the adeno-associated virus (AAV)-α-synuclein into the substantia nigra. This was followed 13 weeks later by delivery of rotenone into the same site. The effect of the genetic and environmental insults alone or in combination on lateralised motor performance (Corridor, Stepping, and Whisker Tests), nigrostriatal integrity (tyrosine hydroxylase immunohistochemistry), and α-synucleinopathy (α-synuclein immunohistochemistry) was assessed. We found that rats treated with either AAV-α-synuclein or rotenone developed significant motor dysfunction with underlying nigrostriatal neurodegeneration. However, when the genetic and environmental insults were sequentially administered, the detrimental impact of the combined insults on motor performance and nigrostriatal integrity was significantly greater than the impact of either insult alone. This indicates that sequential exposure to relevant genetic and environmental insults is a valid approach to modeling human Parkinson's disease in the rat.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Mulcahy P,O'Doherty A,Paucard A,O'Brien T,Kirik D,Dowd E

doi

10.1016/j.neuroscience.2011.12.011

subject

Has Abstract

pub_date

2012-02-17 00:00:00

pages

170-9

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(11)01391-1

journal_volume

203

pub_type

杂志文章

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