RGD Reference Report - Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson's disease. - Rat Genome Database

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Genetic disruption of the nuclear receptor Nur77 (Nr4a1) in rat reduces dopamine cell loss and l-Dopa-induced dyskinesia in experimental Parkinson's disease.

Authors: Rouillard, Claude  Baillargeon, Joanie  Paquet, Brigitte  St-Hilaire, Michel  Maheux, Jérôme  Lévesque, Catherine  Darlix, Noémie  Majeur, Simon  Lévesque, Daniel 
Citation: Rouillard C, etal., Exp Neurol. 2018 Jun;304:143-153. doi: 10.1016/j.expneurol.2018.03.008. Epub 2018 Mar 9.
RGD ID: 40924655
Pubmed: PMID:29530712   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2018.03.008   (Journal Full-text)

Parkinson's disease (PD) is an idiopathic progressive neurodegenerative disorder characterized by the loss of midbrain dopamine neurons. Levodopa (l-dopa) is the main pharmacological approach to relieve PD motor symptoms. However, chronic treatment with l-Dopa is inevitably associated with the generation of abnormal involuntary movements (l-Dopa-induced dyskinesia). We have previously shown that Nr4a1 (Nur77), a transcription factor of the nuclear receptor family, is closely associated with dopamine neurotransmission in the mature brain. However, the role of Nr4a1 in the etiology of PD and its treatment remain elusive. We report here that the neurotoxin 6-hydroxydopamine in rat lead to a rapid up-regulation of Nr4a1 in the substantia nigra. Genetic disruption of Nr4a1 in rat reduced neurotoxin-induced dopamine cell loss and l-Dopa-induced dyskinesia, whereas virally-driven striatal overexpression of Nr4a1 enhanced or partially restored involuntary movements induced by chronic l-Dopa in wild type and Nr4a1-deficient rats, respectively. Collectively, these results suggest that Nr4a1 is involved in dopamine cell loss and l-Dopa-induced dyskinesia in experimental PD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FHH-Nr4a1m1McwiRatDyskinesias treatmentIMPoxidopamine and neuromodulationcompared to wild-type and untreatedRGD 
NR4A1HumanDyskinesias treatmentISONr4a1 (Rattus norvegicus)compared to wild-type and untreatedRGD 
Nr4a1RatDyskinesias treatmentIMPoxidopamine and neuromodulationcompared to wild-type and untreatedRGD 
Nr4a1MouseDyskinesias treatmentISONr4a1 (Rattus norvegicus)compared to wild-type and untreatedRGD 
Nr4a1m1McwiRatDyskinesias treatmentIMPoxidopamine and neuromodulationcompared to wild-type and untreatedRGD 
FHH-Nr4a1m1McwiRatParkinson's disease treatmentIMPoxidopamine and neuromodulationcompared to wild-type and untreatedRGD 
NR4A1HumanParkinson's disease treatmentISONr4a1 (Rattus norvegicus)compared to wild-type and untreatedRGD 
Nr4a1RatParkinson's disease treatmentIMPoxidopamine and neuromodulationcompared to wild-type and untreatedRGD 
Nr4a1MouseParkinson's disease treatmentISONr4a1 (Rattus norvegicus)compared to wild-type and untreatedRGD 
Nr4a1m1McwiRatParkinson's disease treatmentIMPoxidopamine and neuromodulationcompared to wild-type and untreatedRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nr4a1Ratneurotransmitter secretion involved in regulation of skeletal muscle contraction  IMP  RGD 
Nr4a1Ratresponse to amphetamine  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FHH-Nr4a1m1McwiRatabnormal involuntary movement treatmentIMPoxidopamine and neuromodulation RGD 
Nr4a1Ratabnormal involuntary movement treatmentIMPoxidopamine and neuromodulation RGD 
Nr4a1m1McwiRatabnormal involuntary movement treatmentIMPoxidopamine and neuromodulation RGD 
FHH-Nr4a1m1McwiRatabnormal substantia nigra pars compacta morphology inducedIMPoxidopaminecompared to wild-type and untreatedRGD 
Nr4a1Ratabnormal substantia nigra pars compacta morphology  IMP compared to wild-type and untreatedRGD 
Nr4a1m1McwiRatabnormal substantia nigra pars compacta morphology  IMP compared to wild-type and untreatedRGD 
FHH-Nr4a1m1McwiRatenhanced behavioral response to amphetamine inducedIMPneuromodulationcompared to saline-treatedRGD 
Nr4a1Ratenhanced behavioral response to amphetamine  IMP compared to saline-treatedRGD 
Nr4a1m1McwiRatenhanced behavioral response to amphetamine  IMP compared to saline-treatedRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nr4a1  (nuclear receptor subfamily 4, group A, member 1)
Nr4a1m1Mcwi  (nuclear receptor subfamily 4, group A, member 1; mutation 1, Medical College of Wisconsin)

Genes (Mus musculus)
Nr4a1  (nuclear receptor subfamily 4, group A, member 1)

Genes (Homo sapiens)
NR4A1  (nuclear receptor subfamily 4 group A member 1)

Strains
FHH-Nr4a1m1Mcwi  (NA)


Additional Information