ArticleNeurobiology of disease2022
Rotenone induces regionally distinct α-synuclein protein aggregation and activation of glia prior to loss of dopaminergic neurons in C57Bl/6 mice.
Article in Neurobiology of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 77 citations in OpenAlex.
- Trans-Vitisin B Targets Neuroinflammation, Oxidative Stress, and Tau Pathology to Improve Behavioral Outcomes in a Mouse Model of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2026Article
- Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of αSynuclein aggregation.FEBS open bio · 2026Article
- Dual Neuroprotective and Nephroprotective Effects ofInternational journal of molecular sciences · 2026Article
- Bacteroides coprocola protects dopaminergic neurons in rotenone-induced Parkinson's disease mouse model by modulating gut microbiota dysbiosis and inhibiting the NLRP3 signaling pathway.Translational neurodegeneration · 2026Article
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- Farnesol, a Dietary Sesquiterpene, Attenuates Rotenone-Induced Dopaminergic Neurodegeneration by Inhibiting Oxidative Stress, Inflammation, and Apoptosis via Mediation of Cell Signaling Pathways in Rats.International journal of molecular sciences · 2026Article
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- ALDH1/2 deficiency modulates dieldrin-induced dopaminergic neurodegeneration and reactive glial morphometry in male mice.Frontiers in toxicology · 2026Article
- Parkinsonism Reversal and Dopaminergic Resilience: Lessons from a Rotenone-induced Parkinson's Disease Model.bioRxiv : the preprint server for biology · 2025Article
- Reflections on the NIEHS Virtual Consortium funding mechanism (ViCTER) and what it has taught us about the future of transdisciplinary science.Toxicology · 2025Article
- Unique nigral and cortical pathways implicated by epigenomic and transcriptional analyses in rotenone Parkinson's model.NPJ Parkinson's disease · 2025Article
- Understanding the Pre-Clinical Stages of Parkinson's Disease: Where Are We in Clinical and Research Settings?International journal of molecular sciences · 2025Review
- Sex Specific Effects of Environmental Toxin-Derived Alpha Synuclein on Enteric Neuronal-Epithelial Interactions.Neurogastroenterology and motility · 2025Article
- Gene network analysis combined with preclinical studies to identify and elucidate the mechanism of action of novel irreversible Keap1 inhibitor for Parkinson's disease.Molecular diversity · 2025Article
- Clearance Pathways for α-Synuclein in Parkinson's Disease.Journal of neurochemistry · 2025Review
- Article
- Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection.NPJ Parkinson's disease · 2025Article
- Research models to study lewy body dementia.Molecular neurodegeneration · 2025Review
- Impaired Mitochondrial Function and Ubiquitin Proteasome System Activate α-Synuclein Aggregation in Zinc-Induced Neurotoxicity: Effect of Antioxidants.Journal of molecular neuroscience : MN · 2025Article
- Creatinine production rate is an integrative indicator to monitor muscle status in critically ill patients.Critical care (London, England) · 2025Article
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6 authors at 3 institutions in 1 country.
Funding
Abstract
Rotenone is a naturally occurring insecticide that inhibits mitochondrial complex I and leads to neurochemical and neuropathological deficits closely resembling those in Parkinson's disease (PD). Deficits include loss of dopaminergic neurons (DAn) in the substantia nigra pars compacta (SNpc), decreased dopamine levels and aggregation of misfolded alpha-synuclein (p129). In rat models of rotenone-induced parkinsonism, the progression of neuronal injury has been associated with activation of microglia and astrocytes. However, these neuroinflammatory changes have been challenging to study in mice, in part because the systemic rotenone exposure model utilized in rats is more toxic to mice. To establish a reproducible murine model of rotenone-induced PD, we therefore investigated the progression of neuroinflammation, protein aggregation and DAn loss in C57Bl/6 mice by exposing animals to 2.5 mg/kg/day rotenone for 14 days, followed by a two-week period where neuroinflammation is allowed to progress. Our results indicate that initial cellular dysfunction leads to increased formation of proteinase K-resistant p129 aggregates in the caudate-putamen and SNpc. Clearance of these aggregates was region- and cell type-specific, with the early appearance of reactive astrocytes coinciding with accumulation of p129 in the SNpc. Phagocytic microglial cells containing p129 aggregates were observed proximal to p129
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.