Abstract
BackgroundSelective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. Depressive symptoms are thought to be closely related to neuroinflammation. In this study, we used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants.MethodsPrimary astrocytes were isolated and cultured using neurobasal-based serum-free medium. The cells were treated with a cytokine mixture comprising complement component 1q, tumor necrosis factor α, and interleukin 1α with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed.ResultsAll the SSRIs, including paroxetine, fluoxetine, sertraline, citalopram, and fluvoxamine, show a visible cytotoxicity within the range of applied doses, and a paradoxical effect on astrocytic inflammatory responses as manifested by the promotion of inducible nitric oxide synthase (iNOS) and/or nitric oxide (NO) and the inhibition of interleukin 6 (IL-6) and/or interleukin 1β (IL-1β). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1β but with no impact on iNOS and NO. All the drugs had no regulation on the polarization of astrocytic A1 and A2 types. Mechanisms associated with the antidepressants in astrocytic inflammation route via inhibition of JNK1 activation and STAT3 basal activity.ConclusionsThe study demonstrated that the antidepressants possess differential cytotoxicity to astrocytes and function differently, also paradoxically for the SSRIs, to astrocytic inflammation. Our results provide novel pieces into understanding the differential efficacy and tolerability of the antidepressants in treating patients in the context of astrocytes.
Highlights
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used drugs for depression
Effects of antidepressants on the cytokine mixture (CytoM)-induced inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in primary astrocytes The antidepressants alone did not result in iNOS induction in primary astrocytes
Treatment of citalopram or fluvoxamine led to a gradual upward trend of iNOS expression with significant changes being observed at higher concentrations [citalopram: F(6, 14) = 26.437, p < 0.001; post hoc, e.g., p = 0.012 (CytoM + 40 μM vs CytoM); fluvoxamine: F(6, 14) = 31.368, p < 0.001; post hoc, p < 0.001 (CytoM + 80 μM vs CytoM); Fig. 2D and E]
Summary
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used drugs for depression. A metaanalysis of acute treatment of unipolar major depression in adults indicated differential results of efficacy and acceptability of the new-generation antidepressants. Venlafaxine and sertraline were more efficacious than fluoxetine, fluvoxamine, and paroxetine. Citalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than fluvoxamine, paroxetine, and venlafaxine [1]. In treatment of the major depressive disorder in children and adolescents, only fluoxetine was more effective than placebo, and better in tolerability [2]. For the generalized anxiety disorder, citalopram and venlafaxine were more efficacious and with relatively better acceptability than sertraline and fluoxetine. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used new-generation drugs for depression. We used up-to-date protocols of culture and stimulation and aimed to understand how astrocytes respond to the antidepressants
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
