Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats
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 w...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2018/2682037 |
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| author | Mi Kyoung Seo Young Hoon Kim Roger S. McIntyre Rodrigo B. Mansur Yena Lee Nicole E. Carmona Ah Jeong Choi Gyung-Mee Kim Jung Goo Lee Sung Woo Park |
| author_facet | Mi Kyoung Seo Young Hoon Kim Roger S. McIntyre Rodrigo B. Mansur Yena Lee Nicole E. Carmona Ah Jeong Choi Gyung-Mee Kim Jung Goo Lee Sung Woo Park |
| author_sort | Mi Kyoung Seo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e323d345680f4775915ff22b8e688a16 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-e323d345680f4775915ff22b8e688a162025-02-03T01:31:39ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/26820372682037Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress RatsMi Kyoung Seo0Young Hoon Kim1Roger S. McIntyre2Rodrigo B. Mansur3Yena Lee4Nicole E. Carmona5Ah Jeong Choi6Gyung-Mee Kim7Jung Goo Lee8Sung Woo Park9Paik Institute for Clinical Research, Inje University, Busan, Republic of KoreaDepartment of Psychiatry, Gongju National Hospital, Gongju, Republic of KoreaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaPaik Institute for Clinical Research, Inje University, Busan, Republic of KoreaDepartment of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, Republic of KoreaPaik Institute for Clinical Research, Inje University, Busan, Republic of KoreaPaik Institute for Clinical Research, Inje University, Busan, Republic of KoreaRecent 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.http://dx.doi.org/10.1155/2018/2682037 |
| spellingShingle | Mi Kyoung Seo Young Hoon Kim Roger S. McIntyre Rodrigo B. Mansur Yena Lee Nicole E. Carmona Ah Jeong Choi Gyung-Mee Kim Jung Goo Lee Sung Woo Park Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats Neural Plasticity |
| title | Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats |
| title_full | Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats |
| title_fullStr | Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats |
| title_full_unstemmed | Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats |
| title_short | Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats |
| title_sort | effects of antipsychotic drugs on the epigenetic modification of brain derived neurotrophic factor gene expression in the hippocampi of chronic restraint stress rats |
| url | http://dx.doi.org/10.1155/2018/2682037 |
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