Fluoxetine is a classic antidepressant drug, and its immunomodulatory effects have recently been reported in many disease models. In addition, it has strong anti-neuroinflammatory effects in stroke and neurodegenerative animal models. However, the effect of fluoxetine on microglia phagocytosis and its molecular mechanisms have not yet been studied. In this study, we investigated whether fluoxetine has a regulatory effect on microglial function. Microglia cell lines and primary mouse microglia were treated with fluoxetine, and the production of inflammatory cytokines and neurotrophic factors and the phagocytosis of amyloid beta were measured. Fluoxetine significantly attenuated the production of LPS-induced pro-inflammatory cytokines and oxidative stress in microglia. Fluoxetine also significantly potentiated microglia phagocytosis and autophagy. In addition, autophagy flux inhibitors attenuated fluoxetine-induced phagocytosis. In conclusion, fluoxetine induces autophagy and potentiates phagocytosis in microglia, which can be a novel molecular mechanism of the neuroinflammatory and neuroprotective effects of fluoxetine.

氟西汀是一种经典的抗抑郁药，最近在许多疾病模型中报道了其免疫调节作用。此外，它在中风和神经退行性动物模型中具有很强的抗神经炎症作用。然而，氟西汀对小胶质细胞吞噬作用的影响及其分子机制尚未得到研究。在这项研究中，我们调查了氟西汀是否对小胶质细胞功能具有调节作用。小胶质细胞系和原代小鼠小胶质细胞用氟西汀处理，测量炎症细胞因子和神经营养因子的产生以及淀粉样蛋白的吞噬作用。氟西汀显着减弱小胶质细胞中 LPS 诱导的促炎细胞因子和氧化应激的产生。氟西汀还显着增强了小胶质细胞的吞噬作用和自噬作用。此外，自噬通量抑制剂减弱了氟西汀诱导的吞噬作用。总之，氟西汀在小胶质细胞中诱导自噬并增强吞噬作用，这可能是氟西汀神经炎症和神经保护作用的新分子机制。