Effects of histone acetyltransferase inhibitors on l-DOPA-induced dyskinesia in a murine model of Parkinson's disease
- 주제(키워드) HAT inhibitor , Garcinol , Curcumin , Anacardic acid , L-DOPA-induced dyskinesia , 6-Hydroxydopamine
- 주제(기타) Clinical Neurology; Neurosciences
- 설명문(일반) [Ryu, Young-Kyoung; Park, Hye-Yeon; Go, Jun; Kim, Yong-Hoon; Hwang, Jung Hwan; Choi, Dong-Hee; Noh, Jung-Ran; Lee, Chul-Ho; Kim, Kyoung-Shim] KRIBB, Lab Anim Resource Ctr, Gwahak Ro 125, Daejeon 34141, South Korea; [Ryu, Young-Kyoung; Rhee, Myungchull] Chungnam Natl Univ, Coll Biosci & Biotechnol, Daejeon 34134, South Korea; [Park, Hye-Yeon; Han, Pyung-Lim] Ewha Womans Univ, Dept Brain Sr Cognit Sci, Seoul 03760, South Korea; [Kim, Yong-Hoon; Hwang, Jung Hwan; Lee, Chul-Ho; Kim, Kyoung-Shim] Korea Univ Sci & Technol UST, KRIBB Sch Biosci, Dept Funct Genom, Daejeon 34113, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 SPRINGER WIEN
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000155907
- 본문언어 영어
- Published As http://dx.doi.org/10.1007/s00702-018-1902-4
초록/요약
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.
more