• F Su, H Yi, L Xu, and Z Zhang.
• The Department of Neurology of Affiliated ZhongDa Hospital, The Institute of Neuropsychiatry and Medical School of Southeast University, Nanjing, China.
• Neuroscience. 2015 May 21; 294: 606860-8.

AbstractIncreasing evidence has suggested that microglia dysfunction plays an important role in the pathogenesis of depression. Both classical activation (M1 activation) and alternative activation (M2 activation) may be involved in the process. M1-activated microglia secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to the development of depression, while M2-activated microglia promote tissue reconstruction by releasing anti-inflammatory cytokines involved in the process of depression. Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for depression, and their effects on immune system modulation have recently gained attention. Several studies have suggested that SSRIs affect the M1 activation of microglia, but results have varied. In addition, little is known about the effect of SSRIs on M2 activation in depression. The aim of this study was to investigate the effects of fluoxetine and S-citalopram, two widely used SSRIs in clinical, on both the M1 and M2 activation of microglia (the murine BV2 cell line and mouse primary microglia cell). The indexes of activation were measured by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and Western blot. The present results showed that both fluoxetine and S-citalopram significantly down-regulated the indexes of M1 activation and up-regulated the M2 activation indexes on mRNA and protein levels either in cell line or primary cells. Taken together, the results suggested that fluoxetine and S-citalopram modulated the immune system by inhibiting M1 activation and by improving M2 activation of microglia and that the immune system modulation may partially mediate the therapeutic effects of antidepressant drugs-SSRIs.Copyright © 2015. Published by Elsevier Ltd.

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