Nicotine suppresses crystalline silica‐induced astrocyte activation and neuronal death by inhibiting NF‐κB in the mouse hippocampus.

Autor: Cao, Hangbing, Li, Bing, Mu, Min, Li, Shanshan, Chen, Haoming, Tao, Huihui, Wang, Wenyang, Zou, Yuanjie, Zhao, Yehong, Liu, Yang, Tao, Xinrong
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Zdroj: CNS Neuroscience & Therapeutics; Apr2024, Vol. 30 Issue 4, p1-18, 18p
Abstrakt: Aims: Exposure to crystalline silica (CS) in occupational settings induces chronic inflammation in the respiratory system and, potentially, the brain. Some workers are frequently concurrently exposed to both CS and nicotine. Here, we explored the impact of nicotine on CS‐induced neuroinflammation in the mouse hippocampus. Methods: In this study, we established double‐exposed models of CS and nicotine in C57BL/6 mice. To assess depression‐like behavior, experiments were conducted at 3, 6, and 9 weeks. Serum inflammatory factors were analyzed by ELISA. Hippocampus was collected for RNA sequencing analysis and examining the gene expression patterns linked to inflammation and cell death. Microglia and astrocyte activation and hippocampal neuronal death were assessed using immunohistochemistry and immunofluorescence staining. Western blotting was used to analyze the NF‐κB expression level. Results: Mice exposed to CS for 3 weeks showed signs of depression. This was accompanied by elevated IL‐6 in blood, destruction of the blood–brain barrier, and activation of astrocytes caused by an increased NF‐κB expression in the CA1 area of the hippocampus. The elevated levels of astrocyte‐derived Lcn2 and upregulated genes related to inflammation led to higher neuronal mortality. Moreover, nicotine mitigated the NF‐κB expression, astrocyte activation, and neuronal death, thereby ameliorating the associated symptoms. Conclusion: Silica exposure induces neuroinflammation and neuronal death in the mouse hippocampal CA1 region and depressive behavior. However, nicotine inhibits CS‐induced neuroinflammation and neuronal apoptosis, alleviating depressive‐like behaviors in mice. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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