Neurobiology of Aging xxx (2006) xxx–xxx
Enrichment improves cognition in AD mice by amyloid-related
and unrelated mechanisms
David A. Costa a,b,c, Jennifer R. Cracchiolo a,c,d, Adam D. Bachstetter c,e,
Tiffany F. Hughes b,c, Kelly R. Bales g, Steven M. Paul g, Ronald F. Mervis e,f,
Gary W. Arendash a,c,d, Huntington Potter a,b,c,∗
a Johnnie B. Byrd Sr. Alzheimer’s Center and Research Institute, 15310 Amberly Dr.,Tampa, FL 33647, USA
b Department of Molecular Medicine and Suncoast Gerontology Center, University of South Florida, Tampa, FL 33612, USA
c Florida Alzheimer’s Disease Research Center (NIA), University of South Florida, Tampa, FL 33612, USA
d Memory and Aging Research Laboratory, SCA 110, University of South Florida, Tampa, FL 33620, USA
e Neurostructural Research Laboratories, University Center Dr. Suite 180, Tampa, FL 33612, USA
f Center for Aging and Brain Repair, University of South Florida, Tampa, FL 33612, USA
g Neuroscience Discovery Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA
Received 13 May 2005; received in revised form 31 March 2006; accepted 7 April 2006
A
s
a
B
b
e
a
p
b
©
K
1
t
s
c
[
r
e
0
d
bstract
Lifelong cognitive stimulation is associated with a lower risk of Alzheimer’s disease (AD), but causality is difficult to prove. We therefore
ought to investigate the preventative potential of environmental enrichment (EE) using mice expressing both human mutant presenilin-1
nd the amyloid precursor protein (PS1/PDAPP). At weaning, mice were placed into either an enriched or standard housing environment.
ehavioral testing at 4.5–6 months showed that environmentally enriched PS1/PDAPP mice outperformed mice in standard housing, and were
ehaviorally indistinguishable from non-transgenic mice across multiple cognitive domains. PS1/PDAPP mice exposed to both environmental
nrichment and behavioral testing, but not to EE alone, showed 50% less brain -amyloid without improved dendritic morphology. Microarray
nalysis revealed large enrichment-induced changes in hippocampal expre