Exercise improves cognition and hippocampal plasticity in APOE ɛ4 mice
Open accessAbstract
Background: Human studies on exercise, cognition, and apolipoprotein E (APOE) genotype show that ɛ4 carriers may benefit from regular physical activity. Methods: We examined voluntary wheel‐running, memory, and hippocampal plasticity in APOE ɛ3 and APOE ɛ4 transgenic mice at 10–12 months of age. Results: Sedentary ɛ4 mice exhibited deficits in cognition on the radial‐arm water maze (RAWM), a task dependent on the hippocampus. Six weeks of wheel‐running in ɛ4 mice resulted in improvements on the RAWM to the level of ɛ3 mice. Hippocampal brain‐derived neurotrophic factor (BDNF) levels were similar in ɛ3 and ɛ4 mice, and after exercise BDNF was similarly increased in both ɛ3 and ɛ4 mice. In sedentary ɛ4 mice, tyrosine kinase B (Trk B) receptors were reduced by 50%. Exercise restored Trk B in ɛ4 mice to the level of ɛ3 mice, and in ɛ4 mice, exercise dramatically increased synaptophysin, a marker of synaptic function. Conclusions: Our results support the hypothesis that exercise can improve cognitive function, particularly in ɛ4 carriers.
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Mice with the APOE4 genotype that voluntarily ran in wheels for 6 months had rescued cognitive function and hippocampal BDNF levels, returning them to levels found in APOE3 control mice.
“Mice with the APOE4 genotype that voluntarily ran in wheels for 6 months rescued cognitive function and BDNF levels within the hippocampus by returned them to that found in APOE3 (control) mice (379).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [379]
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- Authors
- Nichol, K., Deeny, S. P., Seif, J., Camaclang, K., & Cotman, C. W.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Nichol, Kathryn
- ORCID
- Cotman, Carl W.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2009-07
- Volume
- 5
- Issue
- 4
- Pages
- 287-294
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4105011
- OpenAlex
- W1986733770
- Cited by
- 213
- References
- 45
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 3 · 2022: 14 · 2021: 7 · 2020: 7 · 2019: 14 · 2018: 16 · 2017: 10 · 2016: 18 · 2015: 17 · 2014: 19 · 2013: 15 · 2012: 24
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AR47752‐06, AG000096‐26)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- physical activity
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Cognition Disorders, Disease Models, Animal, Exercise Therapy, Heterozygote, Hippocampus, Mice, Transgenic, Neural Pathways, Neuronal Plasticity, Physical Conditioning, Animal, Up-Regulation, Synaptophysin, Treatment Outcome, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease, Receptor, trkB, Mice, Apolipoprotein E3, Apolipoprotein E4, Neurogenesis
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