Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice

Orly Lazarov, John Robinson, Ya Ping Tang, Ilana S. Hairston, Zeljka Korade-Mirnics, Virginia M Y Lee, Louis B. Hersh, Robert M. Sapolsky, K. Mirnics, Sangram S. Sisodia

Research output: Contribution to journalArticle

645 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)701-713
Number of pages13
JournalCell
Volume120
Issue number5
DOIs
Publication statusPublished - Mar 11 2005

Fingerprint

Amyloid
Transgenic Mice
Brain
Alzheimer Disease
Up-Regulation
Neprilysin
Endopeptidases
Peptides
Neurogenesis
Amyloid Plaques
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Prostaglandins
Cell Survival
Microarrays
Learning
Animals
Deposits
Genes
Cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Lazarov, O., Robinson, J., Tang, Y. P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M. Y., ... Sisodia, S. S. (2005). Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell, 120(5), 701-713. https://doi.org/10.1016/j.cell.2005.01.015

Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. / Lazarov, Orly; Robinson, John; Tang, Ya Ping; Hairston, Ilana S.; Korade-Mirnics, Zeljka; Lee, Virginia M Y; Hersh, Louis B.; Sapolsky, Robert M.; Mirnics, K.; Sisodia, Sangram S.

In: Cell, Vol. 120, No. 5, 11.03.2005, p. 701-713.

Research output: Contribution to journalArticle

Lazarov, O, Robinson, J, Tang, YP, Hairston, IS, Korade-Mirnics, Z, Lee, VMY, Hersh, LB, Sapolsky, RM, Mirnics, K & Sisodia, SS 2005, 'Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice', Cell, vol. 120, no. 5, pp. 701-713. https://doi.org/10.1016/j.cell.2005.01.015
Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VMY et al. Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. Cell. 2005 Mar 11;120(5):701-713. https://doi.org/10.1016/j.cell.2005.01.015
Lazarov, Orly ; Robinson, John ; Tang, Ya Ping ; Hairston, Ilana S. ; Korade-Mirnics, Zeljka ; Lee, Virginia M Y ; Hersh, Louis B. ; Sapolsky, Robert M. ; Mirnics, K. ; Sisodia, Sangram S. / Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice. In: Cell. 2005 ; Vol. 120, No. 5. pp. 701-713.
@article{69b07baf423a4cb29794b254a0e0f42f,
title = "Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice",
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.",
author = "Orly Lazarov and John Robinson and Tang, {Ya Ping} and Hairston, {Ilana S.} and Zeljka Korade-Mirnics and Lee, {Virginia M Y} and Hersh, {Louis B.} and Sapolsky, {Robert M.} and K. Mirnics and Sisodia, {Sangram S.}",
year = "2005",
month = "3",
day = "11",
doi = "10.1016/j.cell.2005.01.015",
language = "English",
volume = "120",
pages = "701--713",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice

AU - Lazarov, Orly

AU - Robinson, John

AU - Tang, Ya Ping

AU - Hairston, Ilana S.

AU - Korade-Mirnics, Zeljka

AU - Lee, Virginia M Y

AU - Hersh, Louis B.

AU - Sapolsky, Robert M.

AU - Mirnics, K.

AU - Sisodia, Sangram S.

PY - 2005/3/11

Y1 - 2005/3/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=20044377403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20044377403&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2005.01.015

DO - 10.1016/j.cell.2005.01.015

M3 - Article

C2 - 15766532

AN - SCOPUS:20044377403

VL - 120

SP - 701

EP - 713

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -