title: Simvastatin exerts antiamnesic effect in Aβ25-35 -injected mice.
abstract: OBJECTIVE
  Simvastatin (SV) is reported to improve cognition and slow the progression of Alzheimer's disease (AD). This study explored the mechanisms underlying the antiamnesic effect of SV in AD using behavior tests, histological examination, western blot analysis, and electrophysiological recording technique in AD model mice created by intracerebroventricular injection (i.c.v.) of Aβ25-35 .
  
  
  RESULTS
  Chronic administration of SV (40 mg/kg/day) for 11 days after Aβ25-35 -injection ameliorated the impairment of acquisition performance and probe trail test in Morris water maze task and alternation behavior in Y maze task in Aβ25-35 -mice. Aβ25-35 -induced apoptosis of hippocampal CA1 pyramidal cells and Aβ25-35 -impaired high-frequency stimulation (HFS)-dependent long-term potentiation (LTP) induction in hippocampal Schaffer collaterale-CA1 synapse were rescued by SV-treatment. SV prevented Aβ25-35 -inhibited protein kinase B (Akt) and extracellular signal-related kinase-2 (ERK2) phosphorylation, which was sensitive to α7 nicotinic acetylcholine receptor (α7nAChR) antagonist MLA. SV-induced neuroprotection was attenuated by MLA or phosphatidylinositol-3-kinase (PI3K) antagonist LY294002. SV-rescued LTP induction was blocked by α7nAChR, PI3K or MAPK/ERK kinase (MEK) antagonist. Finally, the antiamnesia of SV in Aβ25-35 -mice was attenuated by blockage of SV-induced neuroprotection or SV-rescued LTP induction.
  
  
  CONCLUSIONS
  The antiamnesia of SV in Aβ25-35 -mice depends on its neuroprotection and synaptic plasticity improvement.
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, China; Department of Geriatric Neurology, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Zhi
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Zeng
authors.forename: Zi-Hong
authors.initials: ZH
authors.lastname: Lu
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qu
authors.forename: Wei-Xian
authors.initials: WX
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000150:complications*; D000647:Amnesia / Q000188:drug therapy* / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D051058:Oncogene Protein v-akt / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects; D019821:Simvastatin / Q000627:therapeutic use*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D010446:Peptide Fragments; D064569:alpha7 Nicotinic Acetylcholine Receptor; C074636:amyloid beta-protein (25-35); D019821:Simvastatin; D051058:Oncogene Protein v-akt
keywords: Neuroprotection; Simvastatin; Synaptic plasticity; α7 nicotinic acetylcholine receptor; β-amyloid peptide