Dataset Information

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

ABSTRACT:

Background

Selective 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.

Methods

Primary 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 ?, and interleukin 1? with or without pretreatments of antidepressants. Cell viability, phenotypes, inflammatory responses, and the underlying mechanisms were analyzed.

Results

All 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 1? (IL-1?). The SNRI venlafaxine was the least toxic to astrocytes and inhibited the production of IL-6 and IL-1? 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.

Conclusions

The 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.

SUBMITTER: He JH

PROVIDER: S-EPMC7890881 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

He Jia-Hui JH Liu Rong-Pei RP Peng Yi-Man YM Guo Qing Q Zhu Lan-Bing LB Lian Yi-Zhi YZ Hu Bei-Lei BL Fan Hui-Hui HH Zhang Xiong X Zhu Jian-Hong JH

Journal of neuroinflammation 20210218 1

<h4>Background</h4>Selective 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.<h4>Methods</h4>Primary astrocytes were isolated and cultured using neurobasal-based serum-free medium. ...[more]

PMID: 33602262

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Dataset Information

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

Background

Methods

Results

Conclusions

Publications

Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.

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