ArticleInternational journal of molecular sciences2019
Earliest Mechanisms of Dopaminergic Neurons Sufferance in a Novel Slow Progressing Ex Vivo Model of Parkinson Disease in Rat Organotypic Cultures of Substantia Nigra.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeting TREM2 for Parkinson's Disease: Where to Go?Frontiers in immunology · 2021Pooled it
- Understanding the Pre-Clinical Stages of Parkinson's Disease: Where Are We in Clinical and Research Settings?International journal of molecular sciences · 2025Review
- Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.International journal of molecular sciences · 2024Article
- Comparative study of bilateral putamen for patients with severe Parkinson's disease detected byQuantitative imaging in medicine and surgery · 2023Article
- Inflammation, Dopaminergic Brain and Bilirubin.International journal of molecular sciences · 2023Review
- Bilirubin Prevents the THInternational journal of molecular sciences · 2022Article
- Bilirubin: A Promising Therapy for Parkinson's Disease.International journal of molecular sciences · 2021Review
- Article
- Comprehensive Perspectives on Experimental Models for Parkinson's Disease.Aging and disease · 2021Review
- Searching for Peripheral Biomarkers in Neurodegenerative Diseases: The Tryptophan-Kynurenine Metabolic Pathway.International journal of molecular sciences · 2020Review
- Oxidative Stress in Parkinson's Disease: Potential Benefits of Antioxidant Supplementation.Oxidative medicine and cellular longevity · 2020Review
- Neuroprotective Effect of Schisandra Chinensis on Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinsonian Syndrome in C57BL/6 Mice.Nutrients · 2019Article
- Auraptene Mitigates Parkinson's Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species.International journal of molecular sciences · 2019Article
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Authors and funding
7 authors.
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Abstract
The current treatments of Parkinson disease (PD) are ineffective mainly due to the poor understanding of the early events causing the decline of dopaminergic neurons (DOPAn). To overcome this problem, slow progressively degenerating models of PD allowing the study of the pre-clinical phase are crucial. We recreated in a short ex vivo time scale (96 h) all the features of human PD (needing dozens of years) by challenging organotypic culture of rat substantia nigra with low doses of rotenone. Thus, taking advantage of the existent knowledge, the model was used to perform a time-dependent comparative study of the principal possible causative molecular mechanisms undergoing DOPAn demise. Alteration in the redox state and inflammation started at 3 h, preceding the reduction in DOPAn number (pre-diagnosis phase). The number of DOPAn declined to levels compatible with diagnosis only at 12 h. The decline was accompanied by a persistent inflammation and redox imbalance. Significant microglia activation, apoptosis, a reduction in dopamine vesicle transporters, and the ubiquitination of misfolded protein clearance pathways were late (96 h, consequential) events. The work suggests inflammation and redox imbalance as simultaneous early mechanisms undergoing DOPAn sufferance, to be targeted for a causative treatment aimed to stop/delay PD.
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