Lipopolysaccharide Upregulates Neuroinflammation, Oxidative Stress Responses, and Peroxiredoxins in Depression Models

脂多糖上调抑郁症模型中的神经炎症、氧化应激反应和过氧化物酶

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Abstract

INTRODUCTION: Depression is a chronic psychiatric disorder and belongs to one of the leading causes of suicide worldwide. Peroxiredoxins (Prdxs) play a critical role in scavenging excess reactive oxygen species (ROS) and mitigating oxidative stress. However, the role and underlying mechanisms of Prdxs in depression have not been fully illustrated. METHODS: We carried out lipopolysaccharide (LPS)-induced ICR depression mice and BV2 cell inflammation models. Seven days after LPS-induction, behaviors in ICR mice were assessed by open field test (OFT), sucrose preference test (SPT), and forced swim test (FST), and inflammatory factors levels in serum were quantified via ELISA. The expression levels of Prdxs were evaluated using immunohistochemistry (IHC), western blotting (WB), and RT-qPCR. In LPS-induced BV2 cells, inflammatory factor levels in the supernatant were measured by ELISA. Nitric oxide (NO) levels were detected by biochemical assay. ROS levels were detected via fluorescence signal intensity. Prdxs expression levels were analyzed using WB and RT-qPCR. RESULTS: In LPS-induced ICR mice serum and BV2 cells supernatant, interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta1 (TGF-β1) levels exhibited significant elevation (p < 0.05). In the hippocampus region of LPS-induced mice and LPS-induced BV2 cells, significant upregulation of Prdx1, Prdx2, Prdx4, and Prdx5 levels was observed (p < 0.05). The ROS and NO levels in LPS-induced BV2 cells also significantly increased (p < 0.05). CONCLUSIONS: This study revealed that Prdx1, Prdx2, Prdx4, and Prdx5 were elevated in depression models, which might relate to the occurrence of neuroinflammation, coupled with upregulation of oxidative stress responses. This study provided new strategies for the treatment of depression.

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