The effect of fluoxetine and escitalopram on the activation of microglia

Abstract

Objective To explore the effect of the selective serotonin reuptake inhibitors (SSRIs): fluoxetine and escitalopram on the activation of microglia. Methods The experiment involved two groups of cells, the cell line (BV2) and primary microglia cell, and each group was divided into five sub-groups, the control group, M1 model group, M2 model group, the fluoxetine group and the escitalopram group.After intervention for 24 hours the inflammation index were measured by RT-PCR, enzyme linked immunosorbent assay（ELISA） and Western blot. Results (1) M1 activation: Detected by RT-PCR, fluoxetine significantly reduced the LPS+INF-γ induced expressions of IL-1β (P=0.001), IL-6 (P<0.01), tumor necrosis factor (TNF-a) ( P=0.016) and inducible nitric oxide synthase (iNOS) (P=0.005) mRNA for BV2. Both fluoxetine and escitalopram significantly reduced the LPS+INF-γ induced expressions of IL-6 (P<0.01 respectively),TNF-a (P=0.018,0.029 respectively) and iNOS (P=0.005 respectively) mRNA for primary cells. Detected by Western blot, both fluoxetine and escitalopram significantly reduced LPS+INF-γ induced expressions of Iba-1 (P<0.01, P=0.002 respectively) and CD86 (P<0.01 respectively) for BV2 cells. For primary microglia cells, both fluoxetine and escitalopram significantly reduced LPS+INF-γ induced expressions of CD86 (P<0.01 respectively). Detected by ELISA, fluoxetine significantly reduced the LPS+INF-γ induced releases of TNF-a (P=0.003) and IL-1β (P=0.002) for BV2 cells. For primary microglia cells, both fluoxetine and escitalopram significantly reduced the LPS+INF-γ induced releases of IL-1β (P<0.01 respectively). The TNF-a releases of escitalopram group ((20.2±1.9) g/L were significantly higher than the model group (11.6±1.1) g/L, P=0.012) . (2) M2 activation: Detected by RT-PCR, fluoxetine significantly improved the IL-4 induced IL-10mRNA expressions for primary cells (P=0.036). Detected by Western blot, fluoxetine significantly improved the IL-4 induced CD206 expressions for BV2 cells (P=0.016) and primary cells (P<0.01). Detected by ELISA, fluoxetine significantly improved the IL-4 induced IL-10 releases for BV2 cells (P=0.044) and primary cells (P<0.01). Conclusions Fluoxetine and escitalopram play a role in immune regulation by affecting the activation of microglia, which might be one of the mechanisms of the SSRIs treatment. Key words: Depression; Microglia; Classical activation; Alternative activation; Selective serotonin reuptake inhibitor