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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Main Authors: Victor Augusto Moraes da Silva, Marília de Souza Dantas, Leonardo Agostinho de Castro Silva, Juliana Garcia Carneiro, Bruno Luiz Fonseca Schamber-Reis
Format: Article
Language:English
Published: Hindawi Limited 2015-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2015/286369
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spelling doaj-5b319111fb5d46aeb17060de29c905fc2020-11-25T00:16:23ZengHindawi LimitedBioMed Research International2314-61332314-61412015-01-01201510.1155/2015/286369286369Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary StudyVictor Augusto Moraes da Silva0Marília de Souza Dantas1Leonardo Agostinho de Castro Silva2Juliana Garcia Carneiro3Bruno Luiz Fonseca Schamber-Reis4Department of Medical Genetics, School of Medical Sciences, CESED/FCM, Avenida Senador Argemiro De Figueiredo 1901, Itararé, 58411-020 Campina Grande, PB, BrazilDepartment of Medical Genetics, School of Medical Sciences, CESED/FCM, Avenida Senador Argemiro De Figueiredo 1901, Itararé, 58411-020 Campina Grande, PB, BrazilDepartment of Medical Genetics, School of Medical Sciences, CESED/FCM, Avenida Senador Argemiro De Figueiredo 1901, Itararé, 58411-020 Campina Grande, PB, BrazilDepartment of Medical Genetics, School of Medical Sciences, CESED/FCM, Avenida Senador Argemiro De Figueiredo 1901, Itararé, 58411-020 Campina Grande, PB, BrazilDepartment of Medical Genetics, School of Medical Sciences, CESED/FCM, Avenida Senador Argemiro De Figueiredo 1901, Itararé, 58411-020 Campina Grande, PB, BrazilSchizophrenia (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.http://dx.doi.org/10.1155/2015/286369
collection DOAJ
language English
format Article
sources DOAJ
author Victor Augusto Moraes da Silva
Marília de Souza Dantas
Leonardo Agostinho de Castro Silva
Juliana Garcia Carneiro
Bruno Luiz Fonseca Schamber-Reis
spellingShingle Victor Augusto Moraes da Silva
Marília de Souza Dantas
Leonardo Agostinho de Castro Silva
Juliana Garcia Carneiro
Bruno Luiz Fonseca Schamber-Reis
Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study
BioMed Research International
author_facet Victor Augusto Moraes da Silva
Marília de Souza Dantas
Leonardo Agostinho de Castro Silva
Juliana Garcia Carneiro
Bruno Luiz Fonseca Schamber-Reis
author_sort Victor Augusto Moraes da Silva
title Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study
title_short Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study
title_full Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study
title_fullStr Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study
title_full_unstemmed Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study
title_sort testosterone depletion induces demethylation of murine reelin promoter cpg dinucleotides: a preliminary study
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2015-01-01
description 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.
url http://dx.doi.org/10.1155/2015/286369
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