title: Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice.
abstract: BACKGROUND
  The role of glial cells, especially microglia and astrocytes, in neuroinflammation and cognition has been studied intensively. Lipopolysaccharide (LPS), a commonly used inducer of neuroinflammation, can cause cognitive impairment. Minocycline is known to possess potent neuroprotective activity, but its effect on LPS-induced cognitive impairment is unknown.
  
  
  OBJECTIVE
  This study aims to investigate the effects of minocycline on LPS-induced cognitive impairment and glial cell activation in mice.
  
  
  METHODS
  Behavioral tests were conducted for cognitive function, immunohistochemistry for microglial and astrocyte response, and quantitative PCR for mRNA expression of proinflammatory cytokines.
  
  
  RESULTS
  Minocycline significantly reversed the decreased spontaneous alternation induced by intrahippocampal administration of LPS in the Y-maze task. In the Morris water maze place navigation test, minocycline decreased the escape latency and distance traveled compared to LPS-treated mice. In the probe test, minocycline-treated mice spent more time in the target quadrant and crossed the platform area more frequently than animals in the LPS-treated group. Minocycline produced a significant decrease in the number of Iba-1- and GFAP-positive hippocampal cells compared to the LPS-treated group. Minocycline-treated mice had significantly reduced hippocampal TNF-α and IL-1β mRNA levels compared with LPS-treated animals. Minocycline caused a significant increase in hippocampal BDNF expression compared to the LPS-treated group.
  
  
  CONCLUSIONS
  Minocycline can attenuate LPS-induced cognitive impairments in mice. This effect may be associated with its action to suppress the activation of microglia and astrocytes and to normalize BDNF expression. Since neuroinflammatory processes and cognitive impairments are implicated in neurodegenerative disorders, minocycline may be a promising candidate for treating such diseases.
authors.affiliation: College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hou
authors.affiliation: The 307th Hospital of Chinese People's Liberation Army, 100071, Beijing, China.|Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, China.
authors.forename: Guanbo
authors.initials: G
authors.lastname: Xie
authors.affiliation: College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China.|Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China.
authors.forename: Guoxun
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Jia
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, China. jinghuaxu2002@tom.com.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Life and Health Sciences, Northeastern University, 110004, Shenyang, China. wangbing@mail.neu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D016207:Cytokines / Q000096:biosynthesis; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006624:Hippocampus; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000096:biosynthesis; D008845:Microinjections; D008911:Minocycline / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C528900:glial fibrillary astrocytic protein, mouse; D008911:Minocycline
keywords: Astrocytes; Cognitive impairment; Lipopolysaccharide; Microglia; Minocycline