Expression levels of the BDNF gene and histone modifications around its promoters in the ventral tegmental area and locus ceruleus of rats during forced abstinence from morphine.

Neurochem Res 2012 Jul 13;37(7):1517-23. Epub 2012 Mar 13.

Department of Biochemistry, Shiraz University of Medical Sciences, P.O. Box 1167, Shiraz, Iran.

Brain-derived neurotrophic factor (BDNF) plays a role in mediating molecular, cellular, and behavioral adaptations underlying drug addiction. Here, we examined the influence of withdrawal from repeated morphine treatment on the expression of BDNF mRNA in the ventral tegmental area (VTA) and locus coeruleus (LC) of the rat brain. We also studied whether alternations in mRNA levels of BDNF in these tissues are associated with histone modifications around promoters II and III of the BDNF gene. Thus, chromatin immunoprecipitation (CHIP) and quantitative (q)-PCR were employed to assess acetylation of histone H3 at K9/K14 and trimethylation of histone H3 at K9. Results of qRT-PCR showed that levels of BDNF mRNA in both VTA and LC were significantly increased 7 days rather than 2 h or 24 h following the last injection of morphine. Consistently, CHIP and qPCR analysis revealed that on day 7 of morphine abstinence, both VTA and LC levels of histone methylation at BDNF promoters II and III of morphine treated rats were significantly lower than control animals. Morphine withdrawal caused only a significant increase in H3 acetylation at the promoter II in the LC. These data demonstrate the involvement of histone H3 methylation in the regulation of gene expression in the VTA and LC of rats during forced abstinence of morphine.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-012-0746-9DOI Listing
July 2012

Publication Analysis

Top Keywords

levels bdnf
12
abstinence morphine
8
bdnf mrna
8
ventral tegmental
8
promoters iii
8
tegmental area
8
modifications promoters
8
histone methylation
8
histone modifications
8
forced abstinence
8
bdnf gene
8
rats forced
8
morphine
7
bdnf
7
histone
6
acetylation histone
4
k9/k14 trimethylation
4
assess acetylation
4
histone k9/k14
4
trimethylation histone
4

Similar Publications