title: Lithium ameliorates lipopolysaccharide-induced microglial activation via inhibition of toll-like receptor 4 expression by activating the PI3K/Akt/FoxO1 pathway.
abstract: 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.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Dong
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Dai
authors.forename: Shunmei
authors.initials: S
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: Gui
authors.forename: Wenjie
authors.initials: W
authors.lastname: Jin
authors.forename: Susu
authors.initials: S
authors.lastname: Zhang
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018692:Antimanic Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D018692:Antimanic Agents; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018021:Lithium Chloride; D016177:Macrophage-1 Antigen; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1