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Effects of histone acetyltransferase inhibitors on l-DOPA-induced dyskinesia in a murine model of Parkinson's disease

Title
Effects of histone acetyltransferase inhibitors on l-DOPA-induced dyskinesia in a murine model of Parkinson's disease
Authors
Ryu, Young-KyoungPark, Hye-YeonGo, JunKim, Yong-HoonHwang, Jung HwanChoi, Dong-HeeNoh, Jung-RanRhee, MyungchullHan, Pyung-LimLee, Chul-HoKim, Kyoung-Shim
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2018
Journal Title
JOURNAL OF NEURAL TRANSMISSION
ISSN
0300-9564JCR Link

1435-1463JCR Link
Citation
JOURNAL OF NEURAL TRANSMISSION vol. 125, no. 9, pp. 1319 - 1331
Keywords
HAT inhibitorGarcinolCurcuminAnacardic acidL-DOPA-induced dyskinesia6-Hydroxydopamine
Publisher
SPRINGER WIEN
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on l-DOPA-induced dyskinesia of Parkinson's disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of l-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model. Anacardic acid 2 mg/kg, garcinol 5 mg/kg, or curcumin 100 mg/kg co-treatment with l-DOPA significantly reduced the axial, limb, and orofacial (ALO) score indicating less dyskinesia with administration of HAT inhibitors in 6-OHDA-lesioned mice. Additionally, l-DOPA's efficacy was not altered by the compounds in the early stage of treatment. The expression levels of c-Fos, Fra-2, and Arc were effectively decreased by administration of HAT inhibitors in the ipsilateral striatum. Our findings indicate that HAT inhibitor co-treatment with l-DOPA may have therapeutic potential for management of l-DOPA-induced dyskinesia in patients with PD.
DOI
10.1007/s00702-018-1902-4
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일반대학원 > 뇌·인지과학과 > Journal papers
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