A highly reproducible rotenone model of Parkinson's disease
By J. Cannon, Victor Tapias, Hye-Mee Na, Anthony S. Honick, R. Drolet, J. Greenamyre. Neurobiology of Disease, 2009
763 citations recorded by the source corpus.
The systemic rotenone model of Parkinson's disease (PD) accurately replicates many aspects of the pathology of human PD and has provided insights into the pathogenesis of PD. The major limitation of the rotenone model has been its variability, both in terms of the percentage of animals that develop a clear-cut nigrostriatal lesion and the extent of that lesion. The goal here was to develop an improved and highly reproducible rotenone model of PD. In these studies, male Lewis rats in three age groups (3, 7 or 12-14 months) were administered rotenone (2.75 or 3.0 mg/kg/day) in a specialized vehicle by daily intraperitoneal injection. All rotenone-treated animals developed bradykinesia, postural instability, and/or rigidity, which were reversed by apomorphine, consistent with a lesion of the nigrostriatal dopamine system. Animals were sacrificed when the PD phenotype became debilitating. Rotenone treatment caused a 45% loss of tyrosine hydroxylase-positive substantia nigra neurons and a commensurate loss of striatal dopamine. Additionally, in rotenone-treated animals, α-synuclein and poly-ubiquitin positive aggregates were observed in dopamine neurons of the substantia nigra. In summary, this version of the rotenone model is highly reproducible and may provide an excellent tool to test new neuroprotective strategies.
Subfields: Cellular and Molecular Neuroscience, Neurology
View Paper: https://www.semanticscholar.org/paper/584afc99e437f6dbc52ed79d5d626c45db547e32
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In Cellular and Molecular Neuroscience
In Neurology
Citations in the corpus
- Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases (2015, background): “…and/or rigidity, reduces the tyrosine hydroxylase-positive neurons in the substance nigra, induces a loss of striatal dopamine, and the accumulation of α-syn and poly-ubiquitin positive aggregates in remaining dopaminergic neurons (Betarbet et al., 2000; Sherer et al., 2003; Cannon et al., 2009).”
- Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease (2011, background): “…rotenone produces loss of striatal dopamine terminals, nigral pathology (a-synuclein- and ubiquitin-positive intracellular inclusions and ~45% cell loss) and a clear parkinsonian phenotype characterized by postural instability and reduced paw reaching in the cylinder test (Cannon et al., 2009).”