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Environmental Enrichment Reduces A Levels and Amyloid Deposition in Transgenic Mice

Contact Information

Keywords

amyloid-beta; Alzheimer’s Disease; environmental enrichment; cortex; hippocampus; immunohistochemistry; microarray

Abstract

Cerebral deposition of β-amyloid (Aβ) peptides is an invariant pathological hallmark in brains of patients with Alzheimer’s disease (AD) and transgenic mice coexpressing familial AD-linked APP and PS1 variants. We now report that exposure of transgenic mice to an “enriched environment” results in pronounced reductions in cerebral Aβ levels and amyloid deposits, compared to animals raised under “standard housing” conditions. The enzymatic activity of an Aβ-degrading endopeptidase, neprilysin, is elevated in the brains of “enriched” mice and inversely correlated with amyloid burden. Moreover, DNA microarray analysis revealed selective upregulation in levels of transcripts encoded by genes associated with learning and memory, vasculogenesis, neurogenesis, cell survival pathways, Aβ sequestration, and prostaglandin synthesis. These studies provide evidence that environmental enrichment leads to reductions in steady-state levels of cerebral Aβ peptides and amyloid deposition and selective upregulation in levels of specific transcripts in brains of transgenic mice.

Citation

Lazarov O, Robinson J, Tang YP, et al. Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice. Cell. 2005;120(5):701-713. doi:10.1016/j.cell.2005.01.015

DOI

10.1016/j.cell.2005.01.015

Model

Animal

Conent Area

Alzheimer's Disease/Dementia

EWB-Related Construct

environmental enrichment

Study Design

Animal Study

Species or Study Population

Mouse

Sex (%Female)

Males

Age (Mean, SD)

6 months

Younger Controls?

No

Longitudinal Data?

No

Sample Size

Interventions

Environment enriched with toys, tunnels, wheels, chewable materials

Ethnicity (%white)

N/A

Inclusion Criteria

N/A

Exclusion Criteria

N/A

EWB Measures

Non-EWB Behavioral
Measures

Physiological Measures

Brain IMaging Modality

Brain IMaging Paradigm

Brain Region/Circuit

Cortex, hippocampus

Biological Measures

Immunohistochemistry, western blot analysis, microarray analysis

Other Neural Measures

None

Data Availability?

Data Avalability Details

Diagnostic Measures

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