title: Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice.
abstract: BACKGROUND
  Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that epsilon4 carriers may benefit from regular physical activity.
  
  
  METHODS
  We examined voluntary wheel-running, memory, and hippocampal plasticity in APOE epsilon3 and APOE epsilon4 transgenic mice at 10-12 months of age.
  
  
  RESULTS
  Sedentary epsilon4 mice exhibited deficits in cognition on the radial-arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel-running in epsilon4 mice resulted in improvements on the RAWM to the level of epsilon3 mice. Hippocampal brain-derived neurotrophic factor (BDNF) levels were similar in epsilon3 and epsilon4 mice, and after exercise BDNF was similarly increased in both epsilon3 and epsilon4 mice. In sedentary epsilon4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in epsilon4 mice to the level of epsilon3 mice, and in epsilon4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function.
  
  
  CONCLUSIONS
  Our results support the hypothesis that exercise can improve cognitive function, particularly in epsilon4 carriers.
authors: Institute for Brain Aging and Dementia, University of California, Irvine, CA, USA. k8nichol@gmail.com
authors: Kathryn
authors: K
authors: Nichol
authors: Sean P
authors: SP
authors: Deeny
authors: Joseph
authors: J
authors: Seif
authors: Kevin
authors: K
authors: Camaclang
authors: Carl W
authors: CW
authors: Cotman
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000818:Animals; D053318:Apolipoprotein E3 / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000379:methods*; D020813:Receptor, trkB / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D019208:Brain-Derived Neurotrophic Factor; D016708:Synaptophysin; D020813:Receptor, trkB