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Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Jankowsky, Joanna L. and Melnikova, Tatiana and Fadale, Daniel J. and Xu, Guilian M. and Slunt, Hilda H. and Gonzales, Victoria and Younkin, Linda H. and Younkin, Steven G. and Borchelt, David R. and Savonenko, Alena V. (2005) Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 25 (21). pp. 5217-5224. ISSN 0270-6474. PMCID PMC4440804. doi:10.1523/JNEUROSCI.5080-04.2005.

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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.

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Additional Information:© 2005 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( The user may not create, compile, publish, host, enable or otherwise make available a mirror site of The Journal of Neuroscience site. This work was supported by grants from the National Institutes of Health (AG06656 and AG15453 to S.G.Y. and K01AG26144 to J.L.J.) the John Douglas French Alzheimer's Foundation (J.L.J.), and the American Health Assistance Foundation (J.L.J.). We thank Henriette van Praag and Fred Gage for kindly donating the enrichment cages; Malcolm Leissring, Dennis Selkoe, and Eddie Koo for generously providing IDE-1 and CT15 antibodies; Gay Rudow for help with stereology; Marshall White for animal care; Irene Chang, Allegra Heinrichs, Julia Hsiao, Johanna Morton, Seung-Hyun Woo, Daniel Lamphier, Marco Boccitto, Kimberly Townsend, and Linda Trinh for animal handling and help with behavioral testing; Andres Collazo for assistance with confocal microscopy; and Andy Groves for helpful discussions. We also thank several anonymous reviewers for thoughtful comments that helped us improve this manuscript. We gratefully acknowledge Takeda Chemical Industries Company, Ltd. for providing antibodies BAN50, BNT77, BA27, and BC05. J.L.J. thanks Eloise Goodhew Barnett for her continued support of this research. We regret that, because of space limitations, we were unable to include citations for many of the original articles on both animal enrichment and human epidemiology. We have attempted to reference the earliest or most significant primary publications followed by review articles in which additional studies are discussed.
Funding AgencyGrant Number
John Douglas French Alzheimer's FoundationUNSPECIFIED
American Health Assistance FoundationUNSPECIFIED
Subject Keywords:Alzheimer’s disease; transgenic mouse; amyloid precursor protein; Aβ; environmental enrichment; cognitive behavior
Issue or Number:21
PubMed Central ID:PMC4440804
Record Number:CaltechAUTHORS:20170721-071843091
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Official Citation:Environmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease Joanna L. Jankowsky, Tatiana Melnikova, Daniel J. Fadale, Guilian M. Xu, Hilda H. Slunt, Victoria Gonzales, Linda H. Younkin, Steven G. Younkin, David R. Borchelt, Alena V. Savonenko Journal of Neuroscience 25 May 2005, 25 (21) 5217-5224; DOI: 10.1523/JNEUROSCI.5080-04.2005
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:79264
Deposited By: Ruth Sustaita
Deposited On:21 Jul 2017 17:51
Last Modified:15 Nov 2021 17:46

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