Aberrant neuro-immune responses are involved in abnormalities of epigenetic mechanisms in schizophrenia.

最近的影像学研究表明，精神分裂症的病理生理与白色物质异常和小胶质细胞活化密切相关。此外，临床试验表明，米诺环素，一种对小胶质细胞活化具有抑制作用的抗生素，可以改善精神分裂症的症状。我们已经报道，不仅非典型抗精神病药物与多巴胺D2受体（D2 R）拮抗剂，但阿立哌唑。一种独特的抗精神病药物，具有D2 R部分激动作用，在体外抑制小胶质细胞活化。因此，抗精神病药物可能对小胶质细胞和少突胶质细胞产生有益的影响，但这些机制尚未阐明。在这里，我们利用小胶质细胞和少突胶质细胞的共培养模型研究了抗精神病药物是否通过抑制小胶质细胞活化来抑制少突胶质细胞损伤。阿立哌唑和米诺环素抑制与干扰素-γ（IFN-γ）激活的小胶质细胞共培养模型中少突胶质细胞的凋亡，而氟哌啶醇，一种传统的抗精神病药物，没有。阿立哌唑和米诺环素抑制IFN-γ激活的小胶质细胞产生肿瘤坏死因子-α（TNF-α）。此外，阿立哌唑和米诺环素减弱小胶质细胞中信号转导和转录激活因子1（STAT 1）的磷酸化。总之，我们的研究结果表明，阿立哌唑和米诺环素可能通过减少小胶质细胞活化引起的少突胶质细胞损伤而具有抗精神病作用。这些结果为精神分裂症的研究提出了一个新的治疗假说。还应进行进一步的体内研究，以确认目前的结果。

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.