Mizoguchi Yoshito, Kato Takahiro A, Horikawa Hideki, Monji Akira
Department of Psychiatry, Faculty of Medicine, Saga University Saga, Japan.
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University Fukuoka, Japan ; Innovation Center for Medical Redox Navigation, Kyushu University Fukuoka, Japan.
Front Cell Neurosci. 2014 Nov 5;8:370. doi: 10.3389/fncel.2014.00370. eCollection 2014.
Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that pathophysiology of schizophrenia is related to the inflammatory responses mediated by microglia. Intracellular Ca(2+) signaling, which is mainly controlled by the endoplasmic reticulum (ER), is important for microglial functions such as release of NO and cytokines, migration, ramification and deramification. In addition, alteration of intracellular Ca(2+) signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca(2+) mobilization in microglial cells. This mini-review article summarizes recent findings on cellular mechanisms underlying the characteristic differences in the actions of antipsychotics on microglial intracellular Ca(2+) signaling and reinforces the importance of the ER of microglial cells as a target of antipsychotics for the treatment of schizophrenia.
小胶质细胞是常驻的固有免疫细胞，当它们在对免疫刺激作出反应而被激活时，会释放许多因子，包括促炎细胞因子、一氧化氮（NO）和神经营养因子。最近的报告表明，精神分裂症的病理生理学与小胶质细胞介导的炎症反应有关。细胞内Ca(2+)信号传导主要由内质网（ER）控制，对于小胶质细胞的功能如NO和细胞因子的释放、迁移、分支和去分支很重要。此外，细胞内Ca(2+)信号传导的改变是精神分裂症病理生理学的基础，而典型或非典型抗精神病药物如何影响小胶质细胞内Ca(2+)的动员仍不清楚。这篇小型综述文章总结了关于抗精神病药物对小胶质细胞内Ca(2+)信号传导作用的特征差异背后的细胞机制的最新发现，并强调了小胶质细胞内质网作为抗精神病药物治疗精神分裂症靶点的重要性。
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