Lithium ameliorates lipopolysaccharide-induced microglial activation via inhibition of toll-like receptor 4 expression by activating the PI3K/Akt/FoxO1 pathway

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• 作者：Hongquan Dong (1)
  Xiang Zhang (1)
  Xiaonan Dai (2)
  Shunmei Lu (1)
  Bo Gui (1)
  Wenjie Jin (1)
  Susu Zhang (1)
  Shu Zhang (3)
  Yanning Qian (1)
  
  1. Department of Anesthesiology ; The First Affiliated Hospital of Nanjing Medical University ; 300 Guangzhou Road ; Nanjing ; Jiangsu ; 210029 ; China
  2. Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University ; 123 Tianfei Lane ; Nanjing ; Jiangsu ; 210004 ; China
  3. Clinical Research Center ; The First Affiliated Hospital of Nanjing Medical University ; Nanjing ; 300 Guangzhou Road ; Nanjing ; Jiangsu ; 210029 ; China
  
• 关键词：FoxO1 ; lithium ; microglia ; PI3K/Akt ; TLR4
• 刊名：Journal of Neuroinflammation
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：11
• 期：1
• 全文大小：1,284 KB
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• 刊物主题：Neurosciences; Neurology; Neurobiology; Immunology;
• 出版者：BioMed Central
• ISSN：1742-2094

文摘

Background Lithium, an effective mood stabilizer for the treatment of bipolar disorders, has been recently suggested to have a role in neuroprotection during neurodegenerative diseases. The pathogenesis of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus, in this study, we aimed to understand the role of lithium in microglial activation and to elucidate the underlying mechanism(s). Methods Primary microglial cells were pretreated with lithium and stimulated with lipopolysaccharide (LPS). The cells were assessed regarding the responses of pro-inflammatory cytokines, and the associated signaling pathways were evaluated. Results Lithium significantly inhibited LPS-induced microglial activation and pro-inflammatory cytokine production. Further analysis showed that lithium could activate PI3K/Akt signaling. Analyses of the associated signaling pathways demonstrated that the lithium pretreatment led to the suppression of LPS-induced toll-like receptor 4 (TLR4) expressions via the PI3K/Akt/FoxO1 pathway. Conclusions This study demonstrates that lithium can inhibit LPS-induced TLR4 expression and microglial activation through the PI3K/Akt/FoxO1 signaling pathway. These results suggest that lithium plays an important role in microglial activation and neuroinflammation-related diseases, which may lead to a new therapeutic strategy for the treatment of neuroinflammation-related disorders.