title: IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation.
abstract: BACKGROUND
  Neuroinflammation is considered a risk factor for impairments in neuronal function and cognition that arise with trauma, infection, and/or disease. IL-17A has been determined to be involved in neurodegenerative diseases such as multiple sclerosis. Recently, IL-17A has been shown to be upregulated in lipopolysaccharide(LPS)-induced systemic inflammation. This study aims to explore the role of IL-17A in LPS-induced neuroinflammation and cognitive impairment.
  
  
  METHODS
  Male Sprague-Dawley (SD) rats were injected intraperitoneally with LPS (500 μg/kg), and IL-17A expression in serum and in the hippocampus was examined 6, 12, 24, and 48 h later. Then, we investigated whether IL-17A-neutralizing antibodies (IL-17A Abs, 1 mg/kg) prevented neuroinflammation and memory dysfunction in aged rats that received LPS (500 μg/kg) injection. In addition, the effect of IL-17A on microglial activation in vitro was determined using ELISA and immunofluorescence.
  
  
  RESULTS
  LPS injection increased the expression of IL-17A in serum and in the hippocampus. IL-17A Abs improved LPS-induced memory impairment. In addition, IL-17A Abs prevented the LPS-induced expression of TNF-α, IL-6 and inflammatory proteins, and of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the activation of microglia in the brain. IL-17A Abs also inhibited the expression of amyloid precursor protein (APP) and BACE1 and increased the expression of the synaptic marker PSD95 in the aged rats treated with LPS. In an in vitro study, we found that recombinant IL-17A could simulate microglial activation and increase production of pro-inflammatory cytokines.
  
  
  CONCLUSIONS
  Taken together, our results suggest that IL-17A was involved in LPS-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. Anti-IL-17A may represent a new therapeutic strategy for the treatment of endotoxemia-induced neuroinflammation and cognitive dysfunction.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. dgsunjie@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. susuzhang@163.com.
authors.forename: Susu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. zx890910@126.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu, People's Republic of China. hotdog100@163.com.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. hongquan_dong@hotmail.com.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People's Republic of China. yanning_qian@aliyun.com.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000627:therapeutic use; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000906:Antibodies; D016207:Cytokines; D020381:Interleukin-17; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II