2. Academic Validation
  3. Differential effects of binge methamphetamine injections on the mRNA expression of histone deacetylases (HDACs) in the rat striatum

Differential effects of binge methamphetamine injections on the mRNA expression of histone deacetylases (HDACs) in the rat striatum

  • Neurotoxicology. 2014 Dec:45:178-84. doi: 10.1016/j.neuro.2014.10.008.
Oluwaseyi Omonijo 1,  Pawaris Wongprayoon 2,  Bruce Ladenheim 1,  Michael T McCoy 1,  Piyarat Govitrapong 2,  Subramaniam Jayanthi 1,  Jean Lud Cadet 3
Affiliations

Affiliations

  • 1 Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, United States.
  • 2 Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Thailand.
  • 3 Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, United States. Electronic address: jcadet@intra.nida.nih.gov.
PMID: 25452209 DOI: 10.1016/j.neuro.2014.10.008
Abstract

Methamphetamine use disorder is characterized by recurrent binge episodes. Humans addicted to methamphetamine experience various degrees of cognitive deficits and show evidence of neurodegenerative processes in the brain. Binge injections of METH to rodents also cause significant toxic changes in the brain. In addition, this pattern of METH injections can alter gene expression in the dorsal striatum. Gene expression is regulated, in part, by histone deacetylation. We thus tested the possibility that METH toxic doses might cause changes in the mRNA levels of histone deacetylases (HDACs). We found that METH did produce significant decreases in the mRNA expression of HDAC8, which is a class I HDAC. METH also decreased expression of HDAC6, HDAC9, and HDAC10 that are class II HDACs. The expression of the class IV HDAC, HDAC11, was also suppressed by METH. The expression of SIRT2, SIRT5, and SIRT6 that are members of class III HDACs was also downregulated by METH injections. Our findings implicate changes in HDAC expression may be an early indicator of impending METH-induced neurotoxicity in the striatum. This idea is consistent with the accumulated evidence that some HDACs are involved in neurodegenerative processes in the brain.

Keywords

Epigenetics; Gene expression; Neurotoxicity; Sirtuins.

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