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

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. Isolatio...

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Published in:Neuroscience 2004, Vol.127 (3), p.601-609
Main Authors: Dong, H., Goico, B., Martin, M., Csernansky, C.A., Bertchume, A., Csernansky, J.G.
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description 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 β-amyloid 42 plaques in Tg2576 mice. Numerous β-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 β-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.
doi_str_mv 10.1016/j.neuroscience.2004.05.040
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ispartof Neuroscience, 2004, Vol.127 (3), p.601-609
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language eng
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source Elsevier
subjects Amyloid beta-Protein Precursor - genetics
Amyloidosis - pathology
Amyloidosis - physiopathology
Animals
Biological and medical sciences
Cell Division
cell proliferation
Dentate Gyrus - drug effects
Dentate Gyrus - pathology
Dentate Gyrus - physiopathology
Disease Models, Animal
fluoxetine
Fluoxetine - pharmacology
Fundamental and applied biological sciences. Psychology
hippocampus
isolation stress
Memory - drug effects
Memory - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
neurogenesis
Serotonin Uptake Inhibitors - pharmacology
Social Isolation
Stress, Psychological - drug therapy
Stress, Psychological - pathology
Stress, Psychological - physiopathology
Vertebrates: nervous system and sense organs
β-amyloid plaques
title Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress
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