title: Atorvastatin in improvement of cognitive impairments caused by amyloid β in mice: involvement of inflammatory reaction.
abstract: BACKGROUND
  The production of inflammatory cytokines resulting from amyloid β (Aβ) is associated with the initiation of Alzheimer's disease (AD). Atorvastatin (ATV) has been reported to improve AD, however, it is unclear how the anti-inflammatory mechanism is linked with its protection against the impairment of spatial cognitive function in AD. The present study was designed to explore what mechanism was possibly involved in the anti-inflammatory pathway in regard to the ATV treatment of AD.
  
  
  METHODS
  We used an AD model induced by the administration of Aβ(25-35) in male C57BL/6 mice and an in vitro culture system to study the protective effects of ATV on the spatial cognitive deficits, hippocampal long-term potentiation (LTP) impairment and inflammatory reaction.
  
  
  RESULTS
  The intragastric administration of ATV (5 mg/kg) in Aβ(25-35)-treated mice significantly ameliorated the spatial cognitive deficits and prevented the LTP impairment in hippocampal CA1. The increased Iba-1 positive cells and inflammatory components in the hippocampus were reduced after the ATV treatment. The anti-inflammatory and LTP protection of ATV were abolished using the replenishment of farnesyl pyrophosphate by the administration of farnesol (FOH). The hippocampal slices culture showed Aβ(25-35)-induced neurotoxicity in the absence of the presence of ATV. Treatment with ATV (0.5, 1, 2.5 μmol/L) dose-dependently prevented the cell damage in hippocampus induced by Aβ25-35.
  
  
  CONCLUSIONS
  The administration of ATV ameliorated the cognitive deficits, depressed the inflammatory responses, improved the LTP impairment, and prevents Aβ25-35-induced neurotoxicity in cultured hippocampal neurons. These protective functions of ATV involved the pathway of reducing farnesyl pyrophosphate (FPP).
authors: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China.|Department of Neurology, The Second Hospital of Huaian, Huaian, Jiangsu, 223002, China.
authors: Liandong
authors: L
authors: Zhao
authors: Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors: Tingting
authors: T
authors: Chen
authors: Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors: Chonghui
authors: C
authors: Wang
authors: Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors: Guoxi
authors: G
authors: Li
authors: Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors: Wenhui
authors: W
authors: Zhi
authors: Department of Physiology, Nanjing Medical University, Nanjing, 210029, China.
authors: Jun
authors: J
authors: Yin
authors: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China. qi_wan@126.com.
authors: Qi
authors: Q
authors: Wan
authors: Department of Physiology, Nanjing Medical University, Nanjing, 210029, China. lingchen@njmu.edu.cn.|Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, China. lingchen@njmu.edu.cn.
authors: Ling
authors: L
authors: Chen
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects; D018782:Maze Learning; D008810:Mice, Inbred C57BL
chemical_list: D016229:Amyloid beta-Peptides; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin