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http://purl.uniprot.org/citations/21085660http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21085660http://www.w3.org/2000/01/rdf-schema#comment"

Background

Dyskinesias associated with involuntary movements and painful muscle contractions are a common and severe complication of standard levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) therapy for Parkinson's disease. Pathologic neuroplasticity leading to hyper-responsive dopamine receptor signaling in the sensorimotor striatum is thought to underlie this currently untreatable condition.

Methodology/principal findings

Quantitative real-time polymerase chain reaction (PCR) was employed to evaluate the molecular changes associated with L-DOPA-induced dyskinesias in Parkinson's disease. With this technique, we determined that thyrotropin releasing hormone (TRH) was greatly increased in the dopamine-depleted striatum of hemi-parkinsonian rats that developed abnormal movements in response to L-DOPA therapy, relative to the levels measured in the contralateral non-dopamine-depleted striatum, and in the striatum of non-dyskinetic control rats. ProTRH immunostaining suggested that TRH peptide levels were almost absent in the dopamine-depleted striatum of control rats that did not develop dyskinesias, but in the dyskinetic rats, proTRH immunostaining was dramatically up-regulated in the striatum, particularly in the sensorimotor striatum. This up-regulation of TRH peptide affected striatal medium spiny neurons of both the direct and indirect pathways, as well as neurons in striosomes.

Conclusions/significance

TRH is not known to be a key striatal neuromodulator, but intrastriatal injection of TRH in experimental animals can induce abnormal movements, apparently through increasing dopamine release. Our finding of a dramatic and selective up-regulation of TRH expression in the sensorimotor striatum of dyskinetic rat models suggests a TRH-mediated regulatory mechanism that may underlie the pathologic neuroplasticity driving dopamine hyper-responsivity in Parkinson's disease."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0013861"xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Landy A."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Standaert D.G."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Crittenden J.R."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Graybiel A.M."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Nillni E.A."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Young A.B."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Keller-McGandy C.E."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Cantuti-Castelvetri I."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Kett L.R."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Hernandez L.F."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Hollingsworth Z.R."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/author"Saka E."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/pages"e13861"xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/title"Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats."xsd:string
http://purl.uniprot.org/citations/21085660http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/21085660http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21085660
http://purl.uniprot.org/citations/21085660http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21085660
http://purl.uniprot.org/uniprot/#_B1WBP2-mappedCitation-21085660http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21085660
http://purl.uniprot.org/uniprot/#_P01150-mappedCitation-21085660http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21085660
http://purl.uniprot.org/uniprot/B1WBP2http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/21085660
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