title: Subcutaneous rotenone rat model of Parkinson's disease: Dose exploration study.
abstract: Subcutaneous administration of rotenone has recently attracted attention because of its convenience, simplicity and efficacy in replicating features of Parkinson's disease (PD) in animal models. However, the wide range of doses reported in the literature makes it difficult to evaluate the effectiveness of this technique objectively. The aim of the present study was to identify the optimum dose of subcutaneous rotenone for establishing a model of PD. We injected male Wistar rats subcutaneously with one of three doses of rotenone (1.5, 2, or 2.5mg/kg) daily for 5 weeks. Rotenone caused a dose-dependent increase in α-synuclein in the substantia nigra. Furthermore, at 2 and 2.5mg/kg, rotenone caused a significant decrease in the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra, and dopamine in the striatum. However, mortality at 2.5mg/kg was 46.7%, compared with just 6.7% at 2mg/kg; the high mortality observed at 2.5mg/kg would limit its application. The 2mg/kg dose showed no detrimental effect on body weight after 5 weeks of daily injections. Furthermore, rats in the 2mg/kg group showed a longer latency to descend from a horizontal bar and a grid wall, decreased rearing, and shorter latency to fall from a rotarod than rats that received vehicle or saline. Mitochondrial damage, observed by transmission electron microscopy, was also evident at this dose. Together, our data indicate that daily subcutaneous injection of 2mg/kg rotenone in rats facilitates the formation of α-synuclein and reproduces the typical features of PD, while maintaining low mortality.
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Zhen-Nian
authors.initials: ZN
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Jing-Si
authors.initials: JS
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Zhong-Hai
authors.initials: ZH
authors.lastname: Yu
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Xiang-Ting
authors.initials: XT
authors.lastname: Li
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Li
authors.affiliation: Department of Integrative Medicine, Zhongshan Hospital, Laboratory of Neurology, Institute of Integrative Medicine, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Electronic address: dingfangcai@163.com.
authors.forename: Ding-Fang
authors.initials: DF
authors.lastname: Cai
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D011897:Random Allocation; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D012402:Rotenone / Q000008:administration & dosage*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: C497606:Snca protein, rat; D051844:alpha-Synuclein; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Animal model; Parkinson's disease; Rotenone; α-synuclein