title: Simvastatin enhances learning and memory independent of amyloid load in mice.
abstract: OBJECTIVE
  Normal aging is often associated with a decline in learning and memory functions. This decline is manifested to a much greater extent in Alzheimer's disease. Recent studies have indicated statins, a class of cholesterol-lowering drugs, as a potential therapy for Alzheimer's disease. Our objective was to determine whether administering a statin drug (simvastatin) would protect against the development of behavioral deficits in an established mouse model of Alzheimer's disease.
  
  
  METHODS
  Tg2576 mice and their nontransgenic littermates were treated with simvastatin and assessed by behavioral tests and biochemical analyses.
  
  
  RESULTS
  Simvastatin treatment not only reversed learning and memory deficits in the Tg2576 mice, but also enhanced learning and memory in the nontransgenic mice. Moreover, levels of amyloid beta protein in the brains of treated mice did not differ from those of untreated mice. Simvastatin treatment was associated with increased expression levels of protein kinase B (Akt) and endothelial nitric oxide synthase in the mouse brain.
  
  
  CONCLUSIONS
  Our findings demonstrate that the effects of simvastatin on learning and memory are independent of amyloid beta protein levels. The mechanisms by which simvastatin exerts its beneficial effects may be related to modulation of signaling pathways in memory formation.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. lili@uab.edu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Cao
authors.forename: Helen
authors.initials: H
authors.lastname: Kim
authors.forename: Robin
authors.initials: R
authors.lastname: Lester
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Fukuchi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D007858:Learning / Q000187:drug effects / Q000502:physiology; D007859:Learning Disabilities / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D018696:Neuroprotective Agents; D002784:Cholesterol; D019821:Simvastatin; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt