Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms.
Lifelong cognitive stimulation is associated with a lower risk of Alzheimer's disease (AD), but causality is difficult to prove. We therefore sought to investigate the preventative potential of environmental enrichment (EE) using mice expressing both human mutant presenilin-1 and the amyloid precursor protein (PS1/PDAPP). At weaning, mice were placed into either an enriched or standard housing environment. Behavioral testing at 4.5-6 months showed that environmentally enriched PS1/PDAPP mice outperformed mice in standard housing, and were behaviorally indistinguishable from non-transgenic mice across multiple cognitive domains. PS1/PDAPP mice exposed to both environmental enrichment and behavioral testing, but not to EE alone, showed 50% less brain beta-amyloid without improved dendritic morphology. Microarray analysis revealed large enrichment-induced changes in hippocampal expression of genes/proteins related to Abeta sequestration and synaptic plasticity. These results indicate that EE protects against cognitive impairment in AD transgenic mice through a dual mechanism, including both amyloid dependent and independent mechanisms.
Costa
David A
DA
Johnnie B. Byrd Sr. Alzheimer's Center and Research Institute, Tampa, FL 33647, USA.
Cracchiolo
Jennifer R
JR
Bachstetter
Adam D
AD
Hughes
Tiffany F
TF
Bales
Kelly R
KR
Paul
Steven M
SM
Mervis
Ronald F
RF
Arendash
Gary W
GW
Potter
Huntington
H
D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D003072:Cognition Disorders / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004777:Environment; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D053764:Presenilin-1 / Q000235:genetics; D020889:Rolipram / Q000627:therapeutic use; D016622:Silver Staining / Q000379:methods
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010726:Phosphodiesterase Inhibitors; D053764:Presenilin-1; D020889:Rolipram