Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study.

Schizophrenia (SZ) is a debilitating mental disorder characterized by psychotic events, abnormal social behavior, false beliefs, and auditory hallucinations. Hypermethylation of the promoter region of reelin (RELN), a gene involved in regulation of neuronal positioning during telencephalic developme...

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Publicado en:BioMed Research International Vol. 2015; pp. 1 - 8
Autores principales: da Silva, Victor Augusto Moraes, Dantas, Marília de Souza, Silva, Leonardo Agostinho de Castro, Carneiro, Juliana Garcia, Schamber-Reis, Bruno Luiz Fonseca
Formato: research tables/charts Journal Article
Publicado: Wiley-Blackwell 10/7/2015
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: BioMed Research International
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      dt: 10/7/2015
      vid: 2015
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2015/286369
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        atl: Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study.
      aug:
        au:
          da Silva, Victor Augusto Moraes
          Dantas, Marília de Souza
          Silva, Leonardo Agostinho de Castro
          Carneiro, Juliana Garcia
          Schamber-Reis, Bruno Luiz Fonseca
        affil: Department of Medical Genetics, School of Medical Sciences, CESED/FCM, Avenida Senador Argemiro De Figueiredo 1901, Itararé, 58411-020 Campina Grande, PB, Brazil
      sug:
        subj:
          Testosterone Metabolism
          Nucleotides Metabolism
          Animal Studies
          Mice
          Models, Biological
          Schizophrenia Physiopathology
          Brain Physiology
          Proteins
          Polymerase Chain Reaction
      ab: Schizophrenia (SZ) is a debilitating mental disorder characterized by psychotic events, abnormal social behavior, false beliefs, and auditory hallucinations. Hypermethylation of the promoter region of reelin (RELN), a gene involved in regulation of neuronal positioning during telencephalic development, is strongly associated with low protein expression in several cortical structures and promoter hypermethylation in brain from postmortem SZ subjects. Recent experimental data suggests that testosterone is able to promote RELN demethylation, although no direct evidence of hormonal influence on reelin promoter methylation was obtained. We investigated if reduced levels of plasma testosterone in adult male mice lead to Reln promoter demethylation. Animals were administered with flutamide, an antiandrogenic compound, and reelin promoter methylation was assessed using methylationspecific PCR using bisulfite DNA from cerebellum. We found that flutamide was able to significantly lower plasma testosterone when compared to control mice, and treatment did not influence animal survival and body weight. We also show that low plasma testosterone was associated with demethylation of a cytosine residue located at -860 in reelin promoter region. These preliminary data suggest that androgenic hormones can influence cerebral reelin demethylation. To our knowledge, this is the first experimental approach directly linking testosterone depletion and RELN promoter methylation.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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