Department of Pharmacology, Medical University of Silesia, Medyków 18, 40-752, Katowice, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2010 Dec;382(5-6):409-17. doi: 10.1007/s00210-010-0535-4. Epub 2010 Sep 2.
An increasing body of evidence indicates that glial activation and neuroinflammation play an important role in the pathogenesis of psychiatric and neurodegenerative diseases. Activated glial cells secrete various cytokines that influence neurotransmission, hypothalamus-pituitary-adrenal axis activity, neuronal plasticity and neurogenesis. It has been suggested that alterations in cytokine networks are involved in the mechanism of action of antidepressant drugs. Until now, only a few studies demonstrated that some tricyclic antidepressants and selective serotonin reuptake inhibitors reduced production of pro-inflammatory cytokines in brain glia cells. We have investigated for the first time whether the antidepressant, moclobemide (a reversible selective inhibitor of monoamine oxidase-A) has an influence on pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory cytokine (IL-10) in primary rat mixed glial cell cultures stimulated by lipopolysaccharide (LPS). Our results showed that moclobemide used in a wide range of concentrations diminished LPS-stimulated IL-1β and TNF-α mRNAs expression in cellular extracts and remarkably reduced the levels of both pro-inflammatory cytokines in culture medium. In opposite to this, the drug had no influence on IL-10 mRNA and slightly reduced IL-10 concentration. Moreover, moclobemide decreased LPS-stimulated translocation of NFκB p65 subunit into cellular nuclei. These results suggest that moclobemide exerts anti-inflammatory effect in the central nervous system because it affects the balance between pro- and anti-inflammatory cytokines (IL-1β, TNF-α/IL-10) in primary mixed glial cell cultures.
越来越多的证据表明，神经胶质细胞的激活和神经炎症在精神疾病和神经退行性疾病的发病机制中起着重要作用。活化的神经胶质细胞分泌各种细胞因子，影响神经递质、下丘脑-垂体-肾上腺轴的活性、神经元的可塑性和神经发生。有人认为细胞因子网络的改变与抗抑郁药的作用机制有关。到目前为止，只有少数研究表明，一些三环类抗抑郁药和选择性 5-羟色胺再摄取抑制剂可以减少脑胶质细胞中促炎细胞因子的产生。我们首次研究了抗抑郁药吗氯贝胺（一种可逆的单胺氧化酶-A 选择性抑制剂）是否对脂多糖（LPS）刺激的原代大鼠混合神经胶质细胞培养物中的促炎细胞因子[白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α]和抗炎细胞因子（IL-10）有影响。我们的结果表明，吗氯贝胺在广泛的浓度范围内可减弱 LPS 刺激的细胞提取物中 IL-1β 和 TNF-α mRNA 的表达，并显著降低培养物中两种促炎细胞因子的水平。与此相反，该药物对 IL-10 mRNA 没有影响，只是略微降低了 IL-10 浓度。此外，吗氯贝胺可减少 LPS 刺激的 NFκB p65 亚基向细胞核内的易位。这些结果表明，吗氯贝胺在中枢神经系统中发挥抗炎作用，因为它影响原代混合神经胶质细胞培养物中促炎和抗炎细胞因子（IL-1β、TNF-α/IL-10）之间的平衡。
