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

  • Young-Kyoung Ryu
  • Hye-Yeon Park
  • Jun Go
  • Yong-Hoon Kim
  • Jung Hwan Hwang
  • Dong-Hee Choi
  • Jung-Ran Noh
  • Myungchull Rhee
  • Pyung-Lim Han
  • Chul-Ho Lee
  • Kyoung-Shim Kim
Neurology and Preclinical Neurological Studies - Original 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.

Keywords

HAT inhibitor Garcinol Curcumin Anacardic acid l-DOPA-induced dyskinesia 6-Hydroxydopamine 

Notes

Acknowledgements

This work was supported by the KRIBB Research Initiative Program of the Republic of Korea, by the Development of Platform Technology for Innovative Medical Measurements Program (No. KRISS-2018-GP2018-0018) from the Korea Research Institute of Standards and Science and by the National Research Foundation of Korea grant funded by the Korea government (MSIT) (No. 2018R1C1B6005079).

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© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory Animal Resource CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)DaejeonRepublic of Korea
  2. 2.College of Biosciences & BiotechnologyChungnam National UniversityDaejeonRepublic of Korea
  3. 3.Department of Brain & Cognitive SciencesEwha Woman’s UniversitySeoulRepublic of Korea
  4. 4.Department of Functional Genomics, KRIBB School of BioscienceKorea University of Science and Technology (UST)DaejeonRepublic of Korea

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