Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-11-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2978093?pdf=render |
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| author | Ippolita Cantuti-Castelvetri Ledia F Hernandez Christine E Keller-McGandy Lauren R Kett Alex Landy Zane R Hollingsworth Esen Saka Jill R Crittenden Eduardo A Nillni Anne B Young David G Standaert Ann M Graybiel |
| author_facet | Ippolita Cantuti-Castelvetri Ledia F Hernandez Christine E Keller-McGandy Lauren R Kett Alex Landy Zane R Hollingsworth Esen Saka Jill R Crittenden Eduardo A Nillni Anne B Young David G Standaert Ann M Graybiel |
| author_sort | Ippolita Cantuti-Castelvetri |
| collection | DOAJ |
| description | 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.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.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. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T01:07:14Z |
| publishDate | 2010-11-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-dc2baa9047584c208c2b171d8395cf7b2022-12-21T19:21:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-11-01511e1386110.1371/journal.pone.0013861Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats.Ippolita Cantuti-CastelvetriLedia F HernandezChristine E Keller-McGandyLauren R KettAlex LandyZane R HollingsworthEsen SakaJill R CrittendenEduardo A NillniAnne B YoungDavid G StandaertAnn M GraybielDyskinesias 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.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.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.http://europepmc.org/articles/PMC2978093?pdf=render |
| spellingShingle | Ippolita Cantuti-Castelvetri Ledia F Hernandez Christine E Keller-McGandy Lauren R Kett Alex Landy Zane R Hollingsworth Esen Saka Jill R Crittenden Eduardo A Nillni Anne B Young David G Standaert Ann M Graybiel Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats. PLoS ONE |
| title | Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats. |
| title_full | Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats. |
| title_fullStr | Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats. |
| title_full_unstemmed | Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats. |
| title_short | Levodopa-induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi-parkinsonian rats. |
| title_sort | levodopa induced dyskinesia is associated with increased thyrotropin releasing hormone in the dorsal striatum of hemi parkinsonian rats |
| url | http://europepmc.org/articles/PMC2978093?pdf=render |
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