title: An update on the rotenone models of Parkinson's disease: their ability to reproduce the features of clinical disease and model gene-environment interactions.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system. Animal models have been invaluable tools for investigating the underlying mechanisms of the pathogenesis of PD and testing new potential symptomatic, neuroprotective and neurorestorative therapies. However, the usefulness of these models is dependent on how precisely they replicate the features of clinical PD with some studies now employing combined gene-environment models to replicate more of the affected pathways. The rotenone model of PD has become of great interest following the seminal paper by the Greenamyre group in 2000 (Betarbet et al., 2000). This paper reported for the first time that systemic rotenone was able to reproduce the two pathological hallmarks of PD as well as certain parkinsonian motor deficits. Since 2000, many research groups have actively used the rotenone model worldwide. This paper will review rotenone models, focusing upon their ability to reproduce the two pathological hallmarks of PD, motor deficits, extranigral pathology and non-motor symptoms. We will also summarize the recent advances in neuroprotective therapies, focusing on those that investigated non-motor symptoms and review rotenone models used in combination with PD genetic models to investigate gene-environment interactions.
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Michaela E
authors.initials: ME
authors.lastname: Johnson
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA 5000, Australia. Electronic address: Larisa.Bobrovskaya@unisa.edu.au.
authors.forename: Larisa
authors.initials: L
authors.lastname: Bobrovskaya
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059647:Gene-Environment Interaction; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology* / Q000235:genetics*; D012402:Rotenone / Q000633:toxicity*
chemical_list: D007306:Insecticides; D012402:Rotenone
keywords: Animal model; Gene–environment interactions; Non-motor symptoms; Parkinson's disease; Rotenone