| Project/Area Number |
16K19786
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Meijo University |
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Principal Investigator |
Ibi Daisuke 名城大学, 薬学部, 助教 (40757514)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 抗精神病薬 / 統合失調症 / HDAC2 / 5-HT2A / 認知機能 / 非定型抗精神病薬 / クロザピン / エピジェネティックス / エピジェネティック |
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| Outline of Final Research Achievements |
Antipsychotic drugs remain the standard for schizophrenia treatment. Despite their effectiveness in treating hallucinations and delusions, prolonged exposure to antipsychotic medications leads to cognitive deficits in both schizophrenia patients and animal models. The molecular mechanisms underlying these negative effects on cognition remain to be elucidated. Here we demonstrate that chronic antipsychotic exposure increases nuclear translocation of NF-kB in mouse frontal cortex, a trafficking event triggered via 5-HT2A-receptor-dependent downregulation of the NF-kB repressor IkBa. This upregulation of NF-kB activity led to its increased binding at the Hdac2 promoter, thereby augmenting Hdac2 transcription. Deletion of HDAC2 in forebrain pyramidal neurons prevented the negative effects of antipsychotic treatment on synaptic remodeling and cognition. Together, these observations may aid in developing therapeutic strategies to improve the outcome of schizophrenia treatment.
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