title: Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson's disease.
abstract: 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.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Xiong
authors.forename: Jinsha
authors.initials: J
authors.lastname: Huang
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xiong
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Chen
authors.forename: Xuebing
authors.initials: X
authors.lastname: Cao
authors.forename: Zhihou
authors.initials: Z
authors.lastname: Liang
authors.forename: Shenggang
authors.initials: S
authors.lastname: Sun
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: 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
chemical_list: D051844:alpha-Synuclein; D012402:Rotenone; D012701:Serotonin; D042967:Electron Transport Complex I; D004298:Dopamine