Risperidone significantly inhibits interferon-γ-induced microglial activation in vitro
Risperidone significantly inhibits interferon-γ-induced microglial activation in vitro
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DOI：
10.1016/j.schres.2007.01.019
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发表时间：
2007-05-01
影响因子：
4.5
通讯作者：
Kanba, Shigenobu
中科院分区：
文献类型：
--
作者：
Kato, Takahiro;Monji, Akira;Kanba, Shigenobu
小胶质细胞最近被认为是神经炎症的中介，通过在中枢神经系统（CNS）中释放促炎细胞因子、一氧化氮（NO）和活性氧（ROS）。因此，小胶质细胞在阿尔茨海默病（AD）和帕金森病（PD）等神经退行性疾病的病理中起着重要作用。精神分裂症的病理机制尚不清楚，而最近的一些神经影像学研究表明，精神分裂症甚至可能是一种神经退行性疾病。据报道，利培酮在精神分裂症的临床过程中减少了MRI体积的减少。最近的许多研究表明，免疫机制如干扰素(IFN)- γ和细胞因子可能与精神分裂症的病理生理有关。在本研究中，我们分别采用Griess法、Western blotting法和ELISA法研究了利培酮对ifn - γ激活的小胶质细胞产生一氧化氮、诱导型NO合成酶（iNOS）表达和炎症细胞因子：白细胞介素(IL)-1 β、IL-6和肿瘤坏死因子(TNF)- α的影响。与氟哌啶醇相比，利珀多酮显著抑制活化小胶质细胞NO和促炎细胞因子的产生。利培酮处理的细胞iNOS水平明显低于氟哌啶醇处理的细胞。抗精神病药物，尤其是利培酮，可能通过抑制小胶质细胞的激活来起到抗炎作用，这不仅对神经元有直接毒性，而且对神经发生和少突胶质发生有抑制作用，这两种作用在精神分裂症的病理中都起着至关重要的作用。(c) 2007 Elsevier B.V.版权所有
Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, rispetidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia. (c) 2007 Elsevier B.V. All rights reserved.