TY - JOUR A2 - Obisesan, Thomas O. AU - da Silva, Victor Augusto Moraes AU - Dantas, MarĂ­lia de Souza AU - Silva, Leonardo Agostinho de Castro AU - Carneiro, Juliana Garcia AU - Schamber-Reis, Bruno Luiz Fonseca PY - 2015 DA - 2015/10/07 TI - Testosterone Depletion Induces Demethylation of Murine Reelin Promoter CpG Dinucleotides: A Preliminary Study SP - 286369 VL - 2015 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. SN - 2314-6133 UR - https://doi.org/10.1155/2015/286369 DO - 10.1155/2015/286369 JF - BioMed Research International PB - Hindawi Publishing Corporation KW - ER -