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Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress.

Abstract：

:Tg2576 transgenic mice (mice overexpressing the "Swedish" mutation in the human amyloid precursor protein 695) demonstrated a decreased capacity for cell proliferation in the dentate gyrus of the hippocampus compared with non-transgenic littermates at 3 months, 6 months and 9 months of age. Isolation stress induced by individually housing each mouse from the time of weaning further decreased hippocampal cell proliferation in Tg2576 mice as well as in non-transgenic littermates at 6 months of age. Decreases in hippocampal cell proliferation in isolated Tg2576 mice were associated with impairments in contextual but not cued memory. Fluoxetine administration increased cell proliferation and improved contextual memory in isolated Tg2576 mice. Further, isolation stress accelerated the age-dependent deposition of beta-amyloid 42 plaques in Tg2576 mice. Numerous beta-amyloid plaques were found in isolated but not non-isolated Tg2576 mice at 6 months of age. These results suggest that Tg2576 mice, a mouse model of Alzheimer disease, have an impaired ability to generate new cells in the dentate gyrus of the hippocampus and that the magnitude of this impairment can be modulated by behavioral interventions and drugs known to have effects on hippocampal neurogenesis in normal rodents. Unexpectedly, isolation stress also appeared to accelerate the underlying process of beta-amyloid plaque deposition in Tg2576 mice. These results suggest that stress may have an impact on the underlying disease process associated with Alzheimer's disease.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Dong H,Goico B,Martin M,Csernansky CA,Bertchume A,Csernansky JG

doi

10.1016/j.neuroscience.2004.05.040

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

601-9

issue

3

eissn

0306-4522

issn

1873-7544

pii

S0306452204004038

journal_volume

127

pub_type

杂志文章

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