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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Dyskinesias treatmentIMPoxidopamine and neuromodulation40924655; 40924655; 40924655compared to wild-type and untreatedRGD 
Dyskinesias treatmentISONr4a1 (Rattus norvegicus)40924655; 40924655compared to wild-type and untreatedRGD 
Parkinson's disease treatmentIMPoxidopamine and neuromodulation40924655; 40924655; 40924655compared to wild-type and untreatedRGD 
Parkinson's disease treatmentISONr4a1 (Rattus norvegicus)40924655; 40924655compared to wild-type and untreatedRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neurotransmitter secretion involved in regulation of skeletal muscle contraction  IMP 40924655 RGD 
response to amphetamine  IMP 40924655 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal involuntary movement treatmentIMPoxidopamine and neuromodulation40924655; 40924655; 40924655 RGD 
abnormal substantia nigra pars compacta morphology inducedIMPoxidopamine40924655compared to wild-type and untreatedRGD 
abnormal substantia nigra pars compacta morphology  IMP 40924655; 40924655compared to wild-type and untreatedRGD 
enhanced behavioral response to amphetamine inducedIMPneuromodulation40924655compared to saline-treatedRGD 
enhanced behavioral response to amphetamine  IMP 40924655; 40924655compared 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