Inhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease

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dc.contributor.authorHye Yeon Park-
dc.contributor.authorYoung Mi Kang-
dc.contributor.authorYoung Kang-
dc.contributor.authorTae Shin Park-
dc.contributor.authorYoung Kyoung Ryu-
dc.contributor.authorJung Hwan Hwang-
dc.contributor.authorYong-Hoon Kim-
dc.contributor.authorBong Hyun Chung-
dc.contributor.authorKi Hoan Nam-
dc.contributor.authorM R Kim-
dc.contributor.authorChul Ho Lee-
dc.contributor.authorP L Han-
dc.contributor.authorKyoung Shim Kim-
dc.date.accessioned2017-04-19T09:55:32Z-
dc.date.available2017-04-19T09:55:32Z-
dc.date.issued2014-
dc.identifier.issn0270-6474-
dc.identifier.uri10.1523/JNEUROSCI.0864-14.2014ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/12135-
dc.description.abstractThe dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is widely used as a therapeutic choice for the treatment of patients with Parkinson's disease. However, the long-term use of L-DOPA leads to the development of debilitating involuntary movements, called L-DOPA-induced dyskinesia (LID). The cAMP/protein kinase A (PKA) signaling in the striatum is known to play a role in LID. However, from among the nine known adenylyl cyclases (ACs) present in the striatum, the AC that mediates LID remains unknown. To address this issue, we prepared an animal model with unilateral 6-hydroxydopamine lesions in the substantia nigra in wild-type and AC5-knock-out (KO) mice, and examined behavioral responses to short-term or long-term treatment with L-DOPA. Compared with the behavioral responses of wild-type mice, LID was profoundly reduced in AC5-KO mice. The behavioral protection of long-term treatment with L-DOPA in AC5-KO mice was preceded by a decrease in the phosphorylation levels of PKA substrates ERK (extracellular signal-regulated kinase) 1/2, MSK1 (mitogen- and stress-activated protein kinase 1), and histone H3, levels of which were all increased in the lesioned striatum of wild-type mice. Consistently, FosB/ΔFosB expression, which was induced by long-term L-DOPA treatment in the lesioned striatum, was also decreased in AC5-KO mice. Moreover, suppression of AC5 in the dorsal striatum with lentivirus-shRNA-AC5 was sufficient to attenuate LID, suggesting that the AC5-regulated signaling cascade in the striatum mediates LID. These results identify the AC5/cAMP system in the dorsal striatum as a therapeutic target for the treatment of LID in patients with Parkinson's disease.-
dc.publisherSoc Neuroscience-
dc.titleInhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease-
dc.title.alternativeInhibition of adenylyl cyclase type 5 prevents L-DOPA-induced dyskinesia in an animal model of Parkinson's disease-
dc.typeArticle-
dc.citation.titleJournal of Neuroscience-
dc.citation.number35-
dc.citation.endPage11753-
dc.citation.startPage11744-
dc.citation.volume34-
dc.contributor.affiliatedAuthorHye Yeon Park-
dc.contributor.affiliatedAuthorYoung Mi Kang-
dc.contributor.affiliatedAuthorYoung Kang-
dc.contributor.affiliatedAuthorTae Shin Park-
dc.contributor.affiliatedAuthorYoung Kyoung Ryu-
dc.contributor.affiliatedAuthorJung Hwan Hwang-
dc.contributor.affiliatedAuthorYong-Hoon Kim-
dc.contributor.affiliatedAuthorBong Hyun Chung-
dc.contributor.affiliatedAuthorKi Hoan Nam-
dc.contributor.affiliatedAuthorChul Ho Lee-
dc.contributor.affiliatedAuthorKyoung Shim Kim-
dc.contributor.alternativeName박혜연-
dc.contributor.alternativeName강영미-
dc.contributor.alternativeName강영-
dc.contributor.alternativeName박태신-
dc.contributor.alternativeName유영경-
dc.contributor.alternativeName황정환-
dc.contributor.alternativeName김용훈-
dc.contributor.alternativeName정봉현-
dc.contributor.alternativeName남기환-
dc.contributor.alternativeName김미리-
dc.contributor.alternativeName이철호-
dc.contributor.alternativeName한평림-
dc.contributor.alternativeName김경심-
dc.identifier.bibliographicCitationJournal of Neuroscience, vol. 34, no. 35, pp. 11744-11753-
dc.identifier.doi10.1523/JNEUROSCI.0864-14.2014-
dc.subject.keywordAdenylyl cyclase-
dc.subject.keywordDyskinesia-
dc.subject.keywordL-DOPA-
dc.subject.keywordParkinson's disease-
dc.subject.localAdenylyl cyclase-
dc.subject.localDyskinesia-
dc.subject.localL-DOPA-
dc.subject.localParkinson's disease-
dc.subject.localParkinsons disease (PD)-
dc.subject.localParkinsons disease-
dc.subject.localParkinson disease-
dc.subject.localParkinson’s diseases-
dc.subject.localParkinson’s Disease-
dc.subject.localParkinson's diasease-
dc.subject.localParkinson’s disease-
dc.description.journalClassY-
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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