ClarifyingtheunderIyingmeGhanismsofschizophreniaviaoxidativestressinthebrain

抗氧化状态的改变与精神分裂症有关。小胶质细胞，自由基的主要来源，如超氧化物(。02-)，在各种脑病理中起着至关重要的作用。抗精神病药物通过调节小胶质细胞超氧化物产生的抗氧化作用从未报道过。因此，我们通过电子自旋共振（ESR）光谱研究了抗精神病药物对PMA刺激的啮齿动物小胶质细胞“02代”的影响，并通过细胞内Ca2+成像和免疫染色研究了其胞内机制。通过共培养实验研究了小胶质细胞活化对神经元的损伤作用。本研究结果提示阿立哌唑可能通过降低小胶质细胞氧化反应和随后的神经元反应而具有精神药物作用，为精神分裂症研究提供了一种新的治疗假设。

Altered antioxidant status has been implicated in schizophrenia. Microglia, major sources of free radicals such as superoxide(. 02-), play crucial roles in various brain pathologies. Antioxidative effects of antipsychotics via modulating microglial superoxide generation have never been reported. Therefore, we herein investigated the effects of antipsychotics on the" 02 generation from phorbol-myristate-acetate(PMA)-stimulated rodent microglia by the electron spin resonance(ESR) spectroscopy and also examined the intracellular mechanism by intracellular Ca2+ imaging and immunostaining. Neuronal damage induced by microglial activation was also investigated by the co-culture experiment.Our results imply that aripiprazole may have psychotropic effects by reducing the microglial oxidative reactions and following neuronal reactions, which puts forward a novel therapeutic hypothesis in schizophrenia research.