ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Sex Differences in Rotenone Sensitivity Reflect the Male-to-Female Ratio in Human Parkinson's Disease Incidence.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 83 citations in OpenAlex.
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- Parkinsonism Reversal and Dopaminergic Resilience: Lessons from a Rotenone-induced Parkinson's Disease Model.bioRxiv : the preprint server for biology · 2025Article
- dVGLUT Is a Mediator of Sex Differences in Dopamine Neuron Mitochondrial Function Across Aging and in a Parkinson's Disease Model.Aging cell · 2025Article
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- Parkinson disease-associated toxic exposures selectively up-regulate vesicular glutamate transporter vGlut2 in a model of human cortical neurons.Molecular biology of the cell · 2025Article
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- Analysis of mortality in Parkinson disease in China: Exploration of recent and future trends.Aging medicine (Milton (N.S.W)) · 2024Article
- Alpha-synuclein-induced stress sensitivity renders the Parkinson's disease brain susceptible to neurodegeneration.Acta neuropathologica communications · 2024Article
- Lack of detectable sex differences in the mitochondrial function of Caenorhabditis elegans.BMC ecology and evolution · 2024Article
- The role of autophagy in Parkinson's disease: a gender difference overview.Frontiers in pharmacology · 2024Review
- Developmental exposure to the Parkinson's disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Transient exposure to rotenone causes degeneration and progressive parkinsonian motor deficits, neuroinflammation, and synucleinopathy.NPJ Parkinson's disease · 2023Article
- Inhibition of carnitine palmitoyl-transferase 1 is a potential target in a mouse model of Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
- Burden of Parkinson Disease in China, 1990-2019: Findings from the 2019 Global Burden of Disease Study.Neuroepidemiology · 2023Article
- New insights in animal models of neurotoxicity-induced neurodegeneration.Frontiers in neuroscience · 2023Review
- Sex Differences in Dopaminergic Vulnerability to Environmental Toxicants - Implications for Parkinson's Disease.Current environmental health reports · 2022Review
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5 authors at 1 institution in 2 countries.
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Abstract
There is a critical need to include female subjects in disease research; however, in Parkinson's disease, where the male-to-female incidence is about 1.5-to-1, the majority of preclinical research is conducted in male animals. The mitochondrial complex I inhibitor, rotenone, is selectively toxic to dopaminergic neurons, and reproduces several neuropathological features of Parkinson's disease, including α-synuclein pathology. Rotenone has been primarily utilized in male Lewis rats; however, pilot studies in age-matched female Lewis rats revealed that our usual dose (2.8 mg/kg/day intraperitoneal [i.p.]) did not cause dopaminergic neurodegeneration. Therefore, we compared rotenone-treated males (2.8 mg/kg/day, i.p.) to females at increasing doses (2.8 mg/kg/day, 3.2 mg/kg/day, 3.6 mg/kg/day, and 1.6 mg/kg bis in die, i.p.). Female rats receiving 3.2 mg/kg, and 3.6 mg/kg rotenone displayed significant loss of dopaminergic neurons in the substantia nigra as assessed by stereology, which was accompanied by a loss of striatal dopaminergic terminals. Even at these higher doses, however, females showed less inflammation, and less accumulation of α-synuclein and transferrin, possibly as a result of preserved autophagy. Thus, the bias toward increased male incidence of human Parkinson's disease is reflected in the rotenone model. Whether such sex differences will translate into differences in responses to mechanism-driven therapeutic interventions remains to be determined.
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