Exercise improves cognition and hippocampal plasticity in APOE epsilon4 mice.

Full 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.

Author information

Author/s: Nichol, Kathryn (K); Deeny, Sean P (SP); Seif, Joseph (J); Camaclang, Kevin (K); Cotman, Carl W (CW);

Affiliation: Institute for Brain Aging and Dementia, University of California, Irvine, CA, USA. k8nichol(-atsign-)gmail.com

Grants: AG000096-26 (Agency:NIA NIH HHS) ; AR47752-06 (Agency:NIAMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement), published in United States. (Language: eng)

Reference: 2009-Jul; vol 5 (issue 4) : pp 287-94

Dates: Created 2009/06/29; Completed 2009/09/22;

PMID: 19560099, status: MEDLINE (last retrieved date: 9/22/2009)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Alzheimer Disease - genetics; metabolism; therapy
Animals
Apolipoprotein E3 - metabolism
Apolipoprotein E4 - genetics
Brain-Derived Neurotrophic Factor - metabolism
Cognition - physiology
Cognition Disorders - genetics; metabolism; therapy
Disease Models, Animal
Exercise Therapy - methods
Genetic Predisposition to Disease - genetics
Heterozygote

Hippocampus - physiology
Mice
Mice, Transgenic
Neural Pathways - physiology
Neurogenesis - physiology
Neuronal Plasticity - physiology
Physical Conditioning, Animal - methods
Receptor, trkB - metabolism
Synaptophysin - metabolism
Treatment Outcome
Up-Regulation - physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Apolipoprotein E3 (0) ; Apolipoprotein E4 (0) ; Brain-Derived Neurotrophic Factor (0) ; Synaptophysin (0) ; Receptor, trkB (EC 2.7.1.112)

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