ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Striatal Nurr1 Facilitates the Dyskinetic State and Exacerbates Levodopa-Induced Dyskinesia in a Rat Model of Parkinson's Disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Construct optimization for AAV-mediated human α-syn overexpression, and validation across research settings: Development of a shared tool for the research community.Journal of Parkinson's disease · 2026Article
- Effects of chemogenetic inhibition of serotonergic raphe-striatal neurons on L-DOPA-induced behaviors and neurochemistry in a rat model of Parkinson's disease.Acta neuropathologica communications · 2026Article
- Targeting Nurr1 With Amodiaquine Preserves Dendritic Spines and Cognitive Function After Chronic Cerebral Hypoperfusion.Neural plasticity · 2026Article
- Electroconvulsive Therapy Induces Dopaminergic Axon Regeneration, Corticostriatal Remodeling, and Restoration of Motor Function in Parkinsonian Mice.bioRxiv : the preprint server for biology · 2025Article
- Peripheral immune cell-specific genes in Parkinson's disease uncovered by multi-omics with therapeutic implications.NPJ Parkinson's disease · 2025Article
- Effects of genetic knockdown of the serotonin transporter on established L-DOPA-induced dyskinesia and gene expression in hemiparkinsonian rats.Neuropharmacology · 2025Article
- Assessment of complementary white matter microstructural changes and grey matter atrophy in the 6-OHDA-induced model of Parkinson's disease.Neuroscience · 2025Article
- Alterations in functional and structural connectivity in the 6-OHDA-induced Parkinsonian rat model.Frontiers in neuroscience · 2025Article
- Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.Molecular therapy. Nucleic acids · 2024Article
- Amphiregulin blockade decreases the levodopa-induced dyskinesia in a 6-hydroxydopamine Parkinson's disease mouse model.CNS neuroscience & therapeutics · 2023Article
- Downregulation of striatal CaNeurobiology of disease · 2023Article
- Transcriptome Sequencing Reveal That Rno-Rsf1_0012 Participates in Levodopa-Induced Dyskinesia in Parkinson's Disease Rats via Binding to Rno-mir-298-5p.Brain sciences · 2022Article
- The role of NURR1 in metabolic abnormalities of Parkinson's disease.Molecular neurodegeneration · 2022Review
- Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal prostaglandin E2 modulatory effects.Molecular psychiatry · 2022Article
- Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson's Disease: A Perspective Through Preclinical and Clinical Evidence.Frontiers in pharmacology · 2022Review
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- Circuit Mechanisms of L-DOPA-Induced Dyskinesia (LID).Frontiers in neuroscience · 2021Review
- Striatal Nurr1, but not FosB expression links a levodopa-induced dyskinesia phenotype to genotype in Fisher 344 vs. Lewis hemiparkinsonian rats.Experimental neurology · 2020Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with l-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single-unit recordings and dendritic spine analyses on striatal medium spiny neurons (MSNs) in drug-naïve rAAV-injected male parkinsonian rats. rAAV-GFP injected LID-resistant hemi-parkinsonian Lewis rats displayed mild LID and no induction of striatal Nurr1 despite receiving a high dose of l-DOPA. However, Lewis rats overexpressing Nurr1 developed severe LID. Nurr1 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in l-DOPA-naïve rats striatal rAAV-Nurr1 overexpression (1) increased cortically-evoked firing in a subpopulation of identified striatonigral MSNs, and (2) altered spine density and thin-spine morphology on striatal MSNs; both phenomena mimicking changes seen in dyskinetic rats. Finally, we provide postmortem evidence of Nurr1 expression in striatal neurons of l-DOPA-treated PD patients. Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.
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