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dc.contributor.authorCantuti-Castelvetri, Ippolita
dc.contributor.authorHernandez, Ledia F.
dc.contributor.authorKeller-McGandy, Christine E.
dc.contributor.authorKett, Lauren R.
dc.contributor.authorLandy, Alex
dc.contributor.authorHollingsworth, Zane R.
dc.contributor.authorSaka, Esen
dc.contributor.authorCrittenden, Jill R.
dc.contributor.authorNillni, Eduardo A.
dc.contributor.authorYoung, Anne B.
dc.contributor.authorStandaert, David G.
dc.contributor.authorGraybiel, Ann M.
dc.date.accessioned2019-12-10T11:25:13Z
dc.date.available2019-12-10T11:25:13Z
dc.date.issued2010
dc.identifier.issn1932-6203
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0013861
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978093/
dc.identifier.urihttp://hdl.handle.net/11655/15700
dc.description.abstractBackground 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.
dc.relation.isversionof10.1371/journal.pone.0013861
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleLevodopa-Induced Dyskinesia Is Associated with Increased Thyrotropin Releasing Hormone in the Dorsal Striatum of Hemi-Parkinsonian Rats
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalPLoS ONE
dc.contributor.departmentNöroloji
dc.identifier.volume5
dc.identifier.issue11
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus


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