Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease.
A clinically-related animal model of Parkinson's disease (PD) may enable the elucidation of the etiology of the disease and assist the development of medications. However, none of the current neurotoxin-based models recapitulates the main clinical features of the disease or the pathological hallmarks, such as dopamine (DA) neuron specificity of degeneration and Lewy body formation, which limits the use of these models in PD research. To overcome these limitations, we developed a rat model by stereotaxically (ST) infusing small doses of the mitochondrial complex-I inhibitor, rotenone, into two brain sites: the right ventral tegmental area and the substantia nigra. Four weeks after ST rotenone administration, tyrosine hydroxylase (TH) immunoreactivity in the infusion side decreased by 43.7%, in contrast to a 75.8% decrease observed in rats treated systemically with rotenone (SYS). The rotenone infusion also reduced the DA content, the glutathione and superoxide dismutase activities, and induced alpha-synuclein expression, when compared to the contralateral side. This ST model displays neither peripheral toxicity or mortality and has a high success rate. This rotenone-based ST model thus recapitulates the slow and specific loss of DA neurons and better mimics the clinical features of idiopathic PD, representing a reliable and more clinically-related model for PD research.
Xiong
Nian
N
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
Huang
Jinsha
J
Zhang
Zhentao
Z
Zhang
Zhaowen
Z
Xiong
Jing
J
Liu
Xingyuan
X
Jia
Min
M
Wang
Fang
F
Chen
Chunnuan
C
Cao
Xuebing
X
Liang
Zhihou
Z
Sun
Shenggang
S
Lin
Zhicheng
Z
Wang
Tao
T
D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D016631:Lewy Bodies; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000008:administration & dosage*; D012701:Serotonin / Q000494:pharmacology; D051844:alpha-Synuclein / Q000096:biosynthesis
D051844:alpha-Synuclein; D012402:Rotenone; D012701:Serotonin; D042967:Electron Transport Complex I; D004298:Dopamine