2012 Fiscal Year Final Research Report
Aberrant neuro-immune responses are involved in abnormalities of epigenetic mechanisms in schizophrenia.
| Project/Area Number |
23791340
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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 | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | ミクログリア / オリゴデンドロサイト / ミノサイクリン / STAT1 / SOCS1 |
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| Research Abstract |
Recent imaging studies have indicated that the pathophysiology of schizophrenia is closely related to white matter abnormalities and microglial activation. Additionally, clinical trials have suggested that minocycline, an antibiotic with inhibitory effects on microglial activation, improves symptoms of schizophrenia. We have reported that not only atypical antipsychotics with dopamine D2 receptor (D2R) antagonism but also aripiprazole. A unique antipsychotic drug with D2R partial agonism, inhibit microglial activation in vitro. Thus, antipsychotics may exert a beneficial influence on both of microglia and oligodendrocytes, while these mechanisms have not been clarified. Here, we investigated whether antipsychotics suppress oligodendrocyte damage by supressing microglial activation utilizing co-culture model with microglia and oligodendrocytes. Aripiprazole and minocycline suppressed the apoptosis of the oligodendrocytes in the co-culture model with interferon-γ (IFN-γ)-activated microglia, while haloperidol, a traditional antipsychotic drug, did not. Aripiprazole and minocycline inhibited the production of tumor necrosis factor-alpha (TNF-α) from IFN-γ-activated microglia. Moreover, aripiprazole and minocycline attenuated the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in microglia. Overall, our results suggest that aripiprazole and minocycline may have antipsychotic effects through reducing oligodendrocyte damage caused by microglial activation. These results put forward a novel therapeutic hypothesis in schizophrenia research. Future in vivo studies to confirm the present results should also be performed.
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