Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver

Fragou, Domniki; Zanos, Panos; Kouidou, Sofia; Njau, Samuel; Kitchen, Ian; Bailey, Alexis; Kovatsi, Leda

doi:10.1016/j.toxlet.2013.01.022

Cited by 42 publications

(32 citation statements)

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“…DNA methylation at gene promoter sites causes transcriptional silencing and affects the expression of genes that play a role in different biological processes, such as cell adherence, cell cycle, DNA repair, detoxification and apoptosis (Fragou et al, 2007, Richardson, 2003. Therefore, epigenetic phenomena are involved in various disease states and processes, including drug addiction (Schmidt et al, 2013, Hope et al, 2013, Fragou et al, 2013.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetically modified nucleotides in chronic heroin and cocaine treated mice

et al. 2014

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Section: Introductionmentioning

confidence: 99%

“…In a recent study, the global DNA methylation levels in the liver and brain of mice dosed with cocaine and heroin were evaluated (Fragou et al, 2013). This study revealed tissue specific differences in the global methylation status between brain and liver.…”

Section: Introductionmentioning

confidence: 99%

Epigenetically modified nucleotides in chronic heroin and cocaine treated mice

et al. 2014

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“…Consiste na adição de um grupamento metil (CH3) ao carbono da posição cinco da citosina (C), catalizada pela enzima DNA metiltransferase em dinucleotídeos CpG, que são regiões em que uma citosina (C) precede uma guanina (G) na sequência de DNA ('Cfosfato de ligação G') (Figura 6) (Goldberg et al, 2007;Anier et al, 2010;Yuferov et al, 2010;Robison, Nestler, 2011;Feng, Nestler, 2013;Fragou et al, 2013;Nestler, 2014).…”

Section: Epigenéticaunclassified

“…O que sabemos até o momento, é que pode ocorrer de forma ativa ou passiva. A desmetilação ativa ocorre pela ação da enzima demetilase, que remove o grupo CH3 (Robison, Nestler, 2011;Fragou et al, 2013). A forma passiva é realizada pela ação das proteínas de translocação ten-eleven (TET), que reparam a citosina formando a 5-hidroximetilcitosina (5hmC).…”

Section: Fonte: Wong Et Al 2011unclassified

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Estudos epigenéticos em dependentes de crack e cocaína: investigação da metilação global do genoma

Camilo¹

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AGRADECIMENTOSAgradeço primeiramente a Deus pela saúde, fé, perseverança e por iluminar o meu caminho durante esta caminhada.Aos meus pais, Ana Maria e Izilmar, por sua história de sucesso na educação dos filhos diante todas as adversidades. Agradeço pela educação que me deram, pela confiança, pelas broncas e por tudo que fizeram por mim com o objetivo de me formar pessoalmente e profissionalmente.Ao meu irmão, Ronaldo, meu melhor amigo, por seus conselhos, ensinamentos e por acreditar em mim e no meu potencial em todos os momentos. Aos meus familiares, por me incentivar nas horas mais difíceis e nas decisões tomadas, por compartilhar e sempre estar ao meu lado ao longo das minhas conquistas.Aos amigos, aos que se foram e aos que permanecem em minha vida até hoje, por todas as palavras de incentivo e persistência.Ao orientador Professor Doutor Homero Vallada, pelo voto de confiança em me acolher como orientanda. Por sua paciência, experiência e ensinamentos nessa jornada. E, principalmente, por incentivar minha maturidade acadêmica e pessoal. À Banca de qualificação, composta pela Profa. Márcia Scazufca, Prof.Guilherme Messas e Prof. Hermano Tavares, pelas sugestões e orientações adequadas ao aprimoramento dessa pesquisa.

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Increased 5‐hydroxymethylation levels in the hippocampus of rat extinguished from cocaine self‐administration

et al. 2017

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Drug craving and relapse risk during abstinence from cocaine are thought to be caused by persistent changes in transcription and chromatin regulation. Although several brain regions are involved in these processes, the hippocampus seems to play an important role in context-evoked craving and drug-seeking behavior. Only a few studies have examined epigenetic alterations during a period of cocaine abstinence. To investigate the effects of cocaine abstinence on DNA methylation and gene expression, rats that self-administered the drug underwent cocaine abstinence in two time points with extinction training. During the cocaine extinction, we observed elevated global 5-hydroxymethylcytosine(5-hmC) levels with a concurrent increase in Tet3 transcript levels. Moreover, we did not find significant alterations in the levels of Tet3 mRNA and 5-hmC in rats subjected to cocaine abstinence without extinction training. Additionally, our findings demonstrated that the expression of Tet3 target genes was activated. Besides, altered DNA methylation was detected at promoter regions of miRNAs, such as miR-30d and miR-let7i. Further in silico analysis provided evidence that these two molecules targeted the 3' UTR region of the Tet3 gene and thus may contribute to its post-transcriptional regulation. This study has presented novel findings in the hippocampus of rats that underwent extinction training following cocaine self-administration. The alterations in the Tet3 gene expression and the level of 5-hmC may play an important role in extinction learning and the reduction of subsequent cocaine seeking.

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Effect of chronic heroin and cocaine administration on global DNA methylation in brain and liver

Cited by 42 publications

References 50 publications

Epigenetically modified nucleotides in chronic heroin and cocaine treated mice

Epigenetically modified nucleotides in chronic heroin and cocaine treated mice

Estudos epigenéticos em dependentes de crack e cocaína: investigação da metilação global do genoma

Increased 5‐hydroxymethylation levels in the hippocampus of rat extinguished from cocaine self‐administration

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