title: Environment-contact administration of rotenone: A new rodent model of Parkinson's disease.
abstract: Epidemiological studies suggest an association between pesticides and the incidence of Parkinson's disease (PD). Individuals are likely to be exposed to numerous natural or synthetic environmental agents by ingestion, inhalation, or skin contact. Here, we describe a novel environment-contact administration of rotenone model, in which male C57BL/6 mice (15 per group per time-point) were placed in one bedding-free, rotenone-applied cage for 2h every day over a period of 2-6 weeks, mimicking the common ways a person may be exposed to pesticides. Our results showed that rotenone exposure had no detrimental effect on body weights of mice during 6 weeks, nor did it cause systemic toxicity (HPLC analysis of rotenone in blood and brain, as well as complex I activity measurements in brain and muscle), but it caused significant impairments in motor function (open field test, pole test, and rotarod test) from 4 weeks that were responsive to apomorphine. Accordingly, rotenone caused significant dopamine depletion from the striatum (HPLC analysis), nigrostriatal degeneration (quantitative tyrosine hydroxylase immunohistochemistry and western blot), and accumulation of α-synuclein in the substantia nigra and striatum (α-synuclein immunohistochemistry) in a time-dependent manner. In addition, rotenone-exposed mice also developed deficits in gastrointestinal and olfactory function (fecal pellet output and buried food pellet test) prior to the motor dysfunction. Furthermore, we observed that α-synuclein accumulated in the anterior olfactory nucleus and the enteric nervous system at 2 weeks. In summary, this novel rotenone model was able to reproduce many key aspects of PD progression. Therefore, it provides new insight into how environmental factors could trigger PD and provides a useful tool for studying PD pathogenesis and testing neuroprotective strategies.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Lian-Kun
authors.initials: LK
authors.lastname: Song
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Hunan University of Chinese Medicine, Changsha 410208, China.
authors.forename: Shi-Feng
authors.initials: SF
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Yu-He
authors.initials: YH
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Hunan University of Chinese Medicine, Changsha 410208, China. Electronic address: chennh@imm.ac.cn.
authors.forename: Nai-Hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D017615:Enteric Nervous System / Q000473:pathology / Q000503:physiopathology; D004781:Environmental Exposure; D006799:Housing, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055696:Olfactory Perception; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D012402:Rotenone / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; C497605:Snca protein, mouse; D051844:alpha-Synuclein; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine
keywords: Animal model; Environmental exposure; Motor and nonmotor symptoms; Parkinson’s disease; Rotenone; α-Synuclein