title: Atorvastatin prevents amyloid-β peptide oligomer-induced synaptotoxicity and memory dysfunction in rats through a p38 MAPK-dependent pathway.
abstract: OBJECTIVE
  To investigate whether atorvastatin treatment could prevent Aβ1-42 oligomer (AβO)-induced synaptotoxicity and memory dysfunction in rats, and to elucidate the mechanisms involved in the neuroprotective actions of atorvastatin.
  
  
  METHODS
  SD rats were injected with AβOs (5 nmol, icv). The rats were administrated with atorvastatin (10 mg·kg(-1)·d(-1), po) for 2 consecutive weeks (the first dose was given 5 d before AβOs injection). The memory impairments were evaluated with Morris water maze task. The expression of inflammatory cytokines in the hippocampus was determined using ELISA assays. The levels of PSD-95 and p38MAPK proteins in rat hippocampus were evaluated using Western blot analysis. For in vitro experiments, cultured rat hippocampal neurons were treated with AβOs (50 nmol/L) for 48 h. The expression of MAP-2 and synaptophysin in the neurons was detected with immunofluorescence.
  
  
  RESULTS
  The AβO-treated rats displayed severe memory impairments in Morris water maze tests, and markedly reduced levels of synaptic proteins synaptophysin and PSD-95, increased levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and p38MAPK activation in the hippocampus. All these effects were prevented or substantially attenuated by atorvastatin administration. Pretreatment of cultured hippocampal neurons with atorvastatin (1 and 5 μmol/L) concentration-dependently attenuated the AβO-induced synaptotoxicity, including the loss of dendritic marker MAP-2, and synaptic proteins synaptophysin and PSD-95. Pretreatment of the cultured hippocampal neurons with the p38MAPK inhibitor SB203580 (5 μmol/L) blocked the AβO-induced loss of synaptophysin and PSD-95.
  
  
  CONCLUSIONS
  Atorvastatin prevents AβO-induced synaptotoxicity and memory dysfunction through a p38MAPK-dependent pathway.
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Hai-Juan
authors.initials: HJ
authors.lastname: Sui
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Qu
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Sheng-Xue
authors.initials: SX
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002478:Cells, Cultured; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D000069059:Atorvastatin; D048051:p38 Mitogen-Activated Protein Kinases