The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.
Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Open accessAbstract
Epidemiological studies suggest that individuals with greater education or more cognitively demanding occupations have diminished risk of developing dementia. We wanted to test whether this effect could be recapitulated in rodents using environmental enrichment, a paradigm well documented to attenuate behavioral deficits induced by various pathological insults. Here, we demonstrate that learning and memory deficits observed in a transgenic mouse model of Alzheimer's disease can be ameliorated by enrichment. Female transgenic mice overexpressing amyloid precursor protein and/or presenilin-1 and nontransgenic controls were placed into enriched or standard cages at 2 months of age and tested for cognitive behavior after 6 months of differential housing. Enrichment significantly improved performance of all genotypes in the radial water maze and in the classic and repeated-reversal versions of the Morris water maze. However, enrichment did not benefit all genotypes equally. Mice overproducing amyloid-β (Aβ), particularly those with amyloid deposits, showed weaker memory for the platform location in the classic Morris water maze and learned new platform positions in the repeated-reversals task less quickly than their nontransgenic cagemates. Nonetheless, enrichment normalized the performance of Aβ-overproducing mice to the level of standard-housed nontransgenic mice. Moreover, this functional preservation occurred despite increased neuritic plaque burden in the hippocampus of double-transgenic animals and elevated steady-state Aβ levels, because both endogenous and transgene-derived Aβ are increased in enriched animals. These results demonstrate that the generation of Aβ in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“there are many examples of environmental and/or microglial gene manipulation in mouse models of amyloidosis in which cognition improved in the absence of a decrease, or even in the presence of an increase, in plaques.61,62”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
What is cognitive reserve? Theory and research application of the reserve concept
STERN, Y. (2002) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617702813248 · Cited by 3,951
Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880
The Neuroendocrinology of Stress: A Never Ending Story
Lightman, S. L. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01711.x · Cited by 3,588
More hippocampal neurons in adult mice living in an enriched environment
Kempermann, G., Kuhn, H. G., & Gage, F. H. (1997) · Nature · doi:10.1038/386493a0 · Cited by 3,586
Neural consequences of enviromental enrichment
van Praag, H., Kempermann, G., & Gage, F. H. (2000) · Nature Reviews Neuroscience · doi:10.1038/35044558 · Cited by 2,468 · cited 6×
“…with synaptic activity (Kamenetz et al., 2003) to be the most likely explanation for our findings, consistent with the well documented effects of enrichment on neuronal structure and function [see van Praag et al. (2000) for review of enrichment-associated synaptic changes and supplemental Fig.”
BackgroundMethodResultInfluentialAn active and socially integrated lifestyle in late life might protect against dementia
Fratiglioni, L., Paillard-Borg, S., & Winblad, B. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00767-7 · Cited by 2,135
Research works printed but not linked: 4
- 2003, Behav Pharmacol, 14, 419
- 10.1037/0735-7044.107.4.627 · DOI
- 1997, Geriatrics, 52, S50
- Terry R, Katzman RD, Bick KL, Sisodia SS, eds (1999) Alzheimer disease, Ed 2. Philadelphia: Lippincott Williams and Wilkins.
Cited by
Sorted by citations
Enriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265
Mattson, M. P. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00275.x · Cited by 751
Kilgore, M., Miller, C. A., Fass, D. M., Hennig, K. M., Haggarty, S. J., Sweatt, J. D., & Rumbaugh, G. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.197 · Cited by 727
Neurogenesis and Exercise: Past and Future Directions
van Praag, H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8028-z · Cited by 645
Metadata
- Authors
- Jankowsky, J. L., Melnikova, T., Fadale, D. J., Xu, G. M., Slunt, H. H., Gonzales, V., Younkin, L. H., Younkin, S. G., Borchelt, D. R., & Savonenko, A. V.
- Affiliations
- California Institute of Technology (US)
- Johns Hopkins University (US)
- Mayo Clinic in Florida (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-05-25
- Volume
- 25
- Issue
- 21
- Pages
- 5217-5224
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4440804
- OpenAlex
- W2059212904
- Cited by
- 517
- References
- 86
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 14 · 2023: 23 · 2022: 25 · 2021: 27 · 2020: 18 · 2019: 20 · 2018: 27 · 2017: 24 · 2016: 32 · 2015: 34 · 2014: 19 · 2013: 29 · 2012: 26
- FWCI
- 17.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by)
- Funders
- American Health Assistance Foundation
- John Douglas French Alzheimer's Foundation
- National Institutes of Health
- National Institute on Aging (AG 15453, AG06656, K01AG026144, P01AG015453, K01AG26144, R01AG006656)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- environmental enrichment, Alzheimer's disease, amyloid-beta, amyloid precursor protein, presenilin 1, cognitive impairment, learning and memory, Morris water maze, neuritic plaques, hippocampus, transgenic mice
- MeSH terms
- Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Behavior, Animal, Cognition Disorders, Disease Models, Animal, Environment, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Immunohistochemistry, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Time Factors, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Maze Learning, Mice, Presenilin-1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
