Duloxetine ameliorates lipopolysaccharide-induced microglial activation by suppressing iNOS expression in BV-2 microglial cells
Duloxetine ameliorates lipopolysaccharide-induced microglial activation by suppressing iNOS expression in BV-2 microglial cells
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DOI：
10.1007/s00213-022-06194-6
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发表时间：
2022-07
影响因子：
3.4
通讯作者：
Y. Nakatani;Manami Yaguchi;Kazuki Ogino;Risako Noguchi;Naoki Yamamoto;T. Amano
中科院分区：
文献类型：
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作者：
Y. Nakatani;Manami Yaguchi;Kazuki Ogino;Risako Noguchi;Naoki Yamamoto;T. Amano
已知选择性5-羟色胺和5-羟色胺去甲肾上腺素再摄取抑制剂(SSRI，SNRI)都是治疗抑郁症的一线药物。根据单胺假说，SSRI和SNRI均可通过增加突触间隙中单胺的浓度来改善抑郁症的症状。然而，越来越多的证据表明，脑部炎症可能是导致抑郁症的病理生理机制中的一个关键因素。目的在抑郁症等病理条件下，小胶质细胞可能调节炎症反应。本研究旨在探讨度洛西汀能否减轻脂多糖(LPS)诱导的BV-2小胶质细胞炎症反应。度洛西汀可显著降低脂多糖诱导的iNOS蛋白表达水平的升高。此外，脂多糖诱导的磷酸化κBα、磷酸化Akt和Akt蛋白表达水平的升高也显著降低。度洛西汀治疗后，COX-2等促炎因子的蛋白表达水平及I-κ、B、α、Akt等多种分子的磷酸化比率均未发生变化。结论度洛西汀可能具有抗炎作用，可能与其治疗抑郁症的疗效有关。
RationaleIt is known that both selective serotonin and serotonin noradrenaline reuptake inhibitors (SSRI, SNRI) are first-line drugs for the treatment of major depressive disorder. It has also been considered that both SSRI and SNRI can improve the symptoms of major depressive disorder by increasing the concentration of monoamine in the synaptic cleft based on the monoamine hypothesis. However, accumulating evidence has indicated that inflammation in the brain may be a key factor in the pathophysiological mechanisms that underlie the development of major depressive disorder.ObjectivesIt has been advocated that microglial cells may regulate the inflammatory response under pathological conditions such as major depressive disorder. In this study, we focused on whether duloxetine can ameliorate the inflammatory response induced by lipopolysaccharide (LPS) in BV-2 microglial cells.ResultsOur results indicated that duloxetine significantly decreased the NO production induced by LPS. The increase in the protein expression level of iNOS induced by LPS was significantly decreased by treatment with duloxetine. Moreover, the increases in the protein expression levels of phosphorylated-IκBα, phosphorylated-Akt and Akt induced by LPS were also significantly decreased. Unexpectedly, the protein expression levels of other pro-inflammatory factors such as COX-2 and the phosphorylation ratios for various molecules including IκBα and Akt were not changed by treatment with duloxetine.ConclusionsThese findings suggest that duloxetine may have an anti-inflammatory effect, which could contribute to its therapeutic effectiveness for major depressive disorder.