Seo, Mi Kyoung;
Kim, Young Hoon;
McIntyre, Roger S.;
Mansur, Rodrigo B.;
Lee, Yena;
Carmona, Nicole E.;
Choi, Ah Jeong;
Kim, Gyung-Mee;
Lee, Jung Goo;
Park, Sung Woo
Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats
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Medientyp:
E-Artikel
Titel:
Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats
Beteiligte:
Seo, Mi Kyoung;
Kim, Young Hoon;
McIntyre, Roger S.;
Mansur, Rodrigo B.;
Lee, Yena;
Carmona, Nicole E.;
Choi, Ah Jeong;
Kim, Gyung-Mee;
Lee, Jung Goo;
Park, Sung Woo
Erschienen:
Hindawi Limited, 2018
Erschienen in:Neural Plasticity
Sprache:
Englisch
DOI:
10.1155/2018/2682037
ISSN:
2090-5904;
1687-5443
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>Recent studies have shown that antipsychotic drugs have epigenetic effects. However, the effects of antipsychotic drugs on histone modification remain unclear. Therefore, we investigated the effects of antipsychotic drugs on the epigenetic modification of the BDNF gene in the rat hippocampus. Rats were subjected to chronic restraint stress (6 h/d for 21 d) and then were administered with either olanzapine (2 mg/kg) or haloperidol (1 mg/kg). The levels of histone H3 acetylation and MeCP2 binding at BDNF promoter IV were assessed with chromatin immunoprecipitation assays. The mRNA levels of total BDNF with exon IV, HDAC5, DNMT1, and DNMT3a were assessed with a quantitative RT-PCR procedure. Chronic restraint stress resulted in the downregulation of total and exon IV BDNF mRNA levels and a decrease in histone H3 acetylation and an increase in MeCP2 binding at BDNF promoter IV. Furthermore, there were robust increases in the expression of HDAC5 and DNMTs. Olanzapine administration largely prevented these changes. The administration of haloperidol had no effect. These findings suggest that the antipsychotic drug olanzapine induced histone modification of BDNF gene expression in the hippocampus and that these epigenetic alterations may represent one of the mechanisms underlying the actions of antipsychotic drugs.</jats:p>