کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4325301 | 1613990 | 2012 | 11 صفحه PDF | دانلود رایگان |
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by memory loss and impaired cognitive function. One of the hallmarks of AD is the formation of beta amyloid (Aβ) plaques. Aβ has neurodegenerative properties and aggregates in the brain, causing inflammation, oxidative stress and eventually neuronal loss. In AD, adult neurogenesis in the dentate gyrus (DG) of the hippocampus is known to be impaired. We tested how ageing affects neurogenesis and oxidative stress in the commonly used APPSWE/PS1ΔE9 mouse model of AD and their wild type (wt) littermate controls aged 3, 5, 10 and 15 months. Progenitor cell proliferation in the DG of APP/PS1 was lower at 3, 5 and 10 months compared to controls, while oxidative stress in APP/PS1 mice was increased in the cortex at 3 and 5 months of age compared to controls. The numbers of new neurons in the DG were decreased in APP/PS1 mice at 10 and 15 months. In APP/PS1 mice, Aβ plaques were evident in the cortex from 3 months onward; however these were small and few. Plaque size and number consistently increased with age in APP/PS1 mice. These results show that the damage to the brain occurs already very early in the brain, and although neurogenesis is impaired, it is still active even in late stage AD. Therefore, therapies would have the best effects if started early, but promoting neurogenesis may act in a protective and reconstructive way even in later stages of AD.
► Investigation of plaque formation in the brain of a widely used transgenic model of Alzheimer's disease, APPswe/PS-1deltaE9
► Correlation with the development of oxidative stress in different age groups
► Correlation with impairment of neuronal progenitor cell proliferation in the dentate gyrus
► Correlation with impairment in neurogenesis in the granule cell layer of the dentate gyrus
Journal: Brain Research - Volume 1449, 17 April 2012, Pages 83–93