2.50
Hdl Handle:
http://hdl.handle.net/10547/228773
Title:
Striatal histone modifications in models of levodopa-induced dyskinesia.
Authors:
Nicholas, Anthony P.; Lubin, Farah D.; Hallett, Penelope J.; Vattem, Padmapriya; Ravenscroft, Paula; Bezard, Erwan; Zhou, Shaobo; Fox, Susan H.; Brotchie, Jonathan M.; Sweatt, J. David; Standaert, David G.
Abstract:
Despite recent advances in the treatment of Parkinson disease (PD), levodopa remains the most effective and widely used therapy. A major limitation to the use of levodopa is the development of abnormal involuntary movements, termed levodopa-induced dyskinesia (LDID), following chronic levodopa treatment. Since recent studies have suggested that modifications of chromatin structure may be responsible for many long-lasting changes in brain function, we have examined post-translational modifications of striatal histones in two models of LDID: an acute murine model and a chronic macaque monkey model, both exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the primate model, which closely resembles human LDID, we observed that chronic levodopa and the appearance of LDID was associated with marked deacetylation of histone H4, hyperacetylation and dephosphorylation of histone H3, and enhancement of the phosphorylation of extracellular signal-regulated kinase (ERK). In the murine model of acutely rather than chronically induced LDID, dopamine depletion and levodopa treatment also induced deacetylation of histone H4 and phosphorylation of ERK, but histone H3 exhibited decreased trimethylation and reduced rather than enhanced acetylation. These data demonstrate striking changes in striatal histones associated with the induction of LDID in both animal models. The pattern of changes observed, as well as the behavioral features, differed in the two models. However, both models exhibit marked deacetylation of histone H4, suggesting that inhibitors of H4 deacetylation may be useful in preventing or reversing LDID.
Affiliation:
Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, AL 35294-0017, USA. nicholas@uab.edu
Citation:
Striatal histone modifications in models of levodopa-induced dyskinesia. 2008, 106 (1):486-494 J. Neurochem.
Publisher:
Wiley-Blackwell
Journal:
Journal of neurochemistry
Issue Date:
Jul-2008
URI:
http://hdl.handle.net/10547/228773
DOI:
10.1111/j.1471-4159.2008.05417.x
PubMed ID:
18410512
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/18410512
Type:
Article
Language:
en
ISSN:
1471-4159
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorNicholas, Anthony P.en_GB
dc.contributor.authorLubin, Farah D.en_GB
dc.contributor.authorHallett, Penelope J.en_GB
dc.contributor.authorVattem, Padmapriyaen_GB
dc.contributor.authorRavenscroft, Paulaen_GB
dc.contributor.authorBezard, Erwanen_GB
dc.contributor.authorZhou, Shaoboen_GB
dc.contributor.authorFox, Susan H.en_GB
dc.contributor.authorBrotchie, Jonathan M.en_GB
dc.contributor.authorSweatt, J. Daviden_GB
dc.contributor.authorStandaert, David G.en_GB
dc.date.accessioned2012-06-13T11:29:08Z-
dc.date.available2012-06-13T11:29:08Z-
dc.date.issued2008-07-
dc.identifier.citationStriatal histone modifications in models of levodopa-induced dyskinesia. 2008, 106 (1):486-494 J. Neurochem.en_GB
dc.identifier.issn1471-4159-
dc.identifier.pmid18410512-
dc.identifier.doi10.1111/j.1471-4159.2008.05417.x-
dc.identifier.urihttp://hdl.handle.net/10547/228773-
dc.description.abstractDespite recent advances in the treatment of Parkinson disease (PD), levodopa remains the most effective and widely used therapy. A major limitation to the use of levodopa is the development of abnormal involuntary movements, termed levodopa-induced dyskinesia (LDID), following chronic levodopa treatment. Since recent studies have suggested that modifications of chromatin structure may be responsible for many long-lasting changes in brain function, we have examined post-translational modifications of striatal histones in two models of LDID: an acute murine model and a chronic macaque monkey model, both exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the primate model, which closely resembles human LDID, we observed that chronic levodopa and the appearance of LDID was associated with marked deacetylation of histone H4, hyperacetylation and dephosphorylation of histone H3, and enhancement of the phosphorylation of extracellular signal-regulated kinase (ERK). In the murine model of acutely rather than chronically induced LDID, dopamine depletion and levodopa treatment also induced deacetylation of histone H4 and phosphorylation of ERK, but histone H3 exhibited decreased trimethylation and reduced rather than enhanced acetylation. These data demonstrate striking changes in striatal histones associated with the induction of LDID in both animal models. The pattern of changes observed, as well as the behavioral features, differed in the two models. However, both models exhibit marked deacetylation of histone H4, suggesting that inhibitors of H4 deacetylation may be useful in preventing or reversing LDID.en_GB
dc.language.isoenen
dc.publisherWiley-Blackwellen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/18410512en_GB
dc.rightsArchived with thanks to Journal of neurochemistryen_GB
dc.subject.mesh1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-
dc.subject.meshAcetylation-
dc.subject.meshAnimals-
dc.subject.meshChromatin-
dc.subject.meshChromosome Aberrations-
dc.subject.meshCorpus Striatum-
dc.subject.meshDisease Models, Animal-
dc.subject.meshDopamine Agents-
dc.subject.meshDyskinesia, Drug-Induced-
dc.subject.meshExtracellular Signal-Regulated MAP Kinases-
dc.subject.meshFemale-
dc.subject.meshHistones-
dc.subject.meshLevodopa-
dc.subject.meshMacaca mulatta-
dc.subject.meshMale-
dc.subject.meshMethylation-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshParkinsonian Disorders-
dc.subject.meshPhosphorylation-
dc.subject.meshProtein Processing, Post-Translational-
dc.subject.meshSpecies Specificity-
dc.titleStriatal histone modifications in models of levodopa-induced dyskinesia.en
dc.typeArticleen
dc.contributor.departmentCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, AL 35294-0017, USA. nicholas@uab.eduen_GB
dc.identifier.journalJournal of neurochemistryen_GB

Related articles on PubMed

All Items in UOBREP are protected by copyright, with all rights reserved, unless otherwise indicated.