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dc.contributor.author
Jayanthi, Subramaniam
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Gonzalez, Betina
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McCoy, Michael T.
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Ladenheim, Bruce
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Bisagno, Veronica
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Cadet, Jean Lud
dc.date.available
2018-03-28T19:41:10Z
dc.date.issued
2017-08
dc.identifier.citation
Jayanthi, Subramaniam; Gonzalez, Betina; McCoy, Michael T.; Ladenheim, Bruce; Bisagno, Veronica; et al.; Methamphetamine Induces TET1- and TET3-Dependent DNA Hydroxymethylation of Crh and Avp Genes in the Rat Nucleus Accumbens; Humana Press; Molecular Neurobiology; 8-2017; 1-13
dc.identifier.issn
0893-7648
dc.identifier.uri
http://hdl.handle.net/11336/40463
dc.description.abstract
Methamphetamine (METH) addiction is a biopsychosocial disorder that is accompanied by multiple relapses even after prolonged abstinence, suggesting the possibilities of long-lasting maladaptive epigenetic changes in the brain. Here, we show that METH administration produced time-dependent increases in the expression of corticotropin-releasing hormone (Crh/Crf), arginine vasopressin (Avp), and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) mRNAs in the rat nucleus accumbens (NAc). Chromatin immunoprecipitation (ChIP) assays revealed that METH increased the abundance of phosphorylated CREB (pCREB) at the promoter of Cartpt but not at Avp or Crh DNA sequences. In contrast, METH produced DNA hypomethylation at sites near the Crh transcription start site (TSS) and at intragenic Avp sequences. METH also increased DNA hydroxymethylation at the Crh TSS and at intragenic Avp sites. In addition, METH increased the protein expression of ten-eleven-translocation enzymes that catalyze DNA hydroxymethylation. Importantly, METH increased TET1 binding at the Crh promoter and increased TET3 binding at Avp intragenic regions. We further tested the role of TET enzymes in METH-induced changes in gene expression by using the TET inhibitor, 1,5-isoquinolinediol (IQD), and found that IQD blocked METH-induced increases in Crh and Avp mRNA expression. Together, these results indicate that METH produced changes in neuropeptide transcription by both activation of the cAMP/CREB pathway and stimulation of TET-dependent DNA hydroxymethylation. These results provide molecular evidence for epigenetic controls of METH-induced changes in the expression of neuropeptides.
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application/pdf
dc.language.iso
eng
dc.publisher
Humana Press
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Avp
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Cartpt
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Crh
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Dna Hydroxymethylation
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Dna Methylation
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Neuropeptides
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Tet
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Methamphetamine Induces TET1- and TET3-Dependent DNA Hydroxymethylation of Crh and Avp Genes in the Rat Nucleus Accumbens
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-28T14:13:50Z
dc.identifier.eissn
1559-1182
dc.journal.pagination
1-13
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Jayanthi, Subramaniam. National Institutes of Health; Estados Unidos
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Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
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Fil: McCoy, Michael T.. National Institutes of Health; Estados Unidos
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Fil: Ladenheim, Bruce. National Institutes of Health; Estados Unidos
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Fil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina
dc.description.fil
Fil: Cadet, Jean Lud. National Institutes of Health; Estados Unidos
dc.journal.title
Molecular Neurobiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s12035-017-0750-9
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info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s12035-017-0750-9
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