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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

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Abstract

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.

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Acknowledgments

This paper has been extracted from the Ph.D thesis of Farideh Jalali Mashayekhi and was supported by Grant Number 4269 from Vice-chancellor for Research Affairs of Shiraz University of Medical Sciences. We acknowledge the cooperation of Dr Nader Tanideh from the Stem Cell and Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz-Iran.

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Authors and Affiliations

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

    Farideh Jalali Mashayekhi, Mozhgan Rasti, Mostafa Rahvar, Pooneh Mokarram & Ali Akbar Owji

  2. Department of Anatomy, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Reza Namavar

  3. Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Akbar Owji

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  1. Farideh Jalali Mashayekhi
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  2. Mozhgan Rasti
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  3. Mostafa Rahvar
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Correspondence to Ali Akbar Owji.

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Jalali Mashayekhi, F., Rasti, M., Rahvar, M. et al. 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 37, 1517–1523 (2012). https://doi.org/10.1007/s11064-012-0746-9

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  • DOI: https://doi.org/10.1007/s11064-012-0746-9

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