期刊
JOURNAL OF COMPARATIVE NEUROLOGY
卷 525, 期 8, 页码 1797-1810出版社
WILEY
DOI: 10.1002/cne.24156
关键词
Alzheimer's disease; A beta; environmental enrichment; transgenic mouse; brain-derived neurotrophic factor; cognitive function; RRID:SCR_003070; RRID:MGI_3665286; RRID:SCR_002668; RRID:AB_570874; RRID:AB_262185; RRID:AB_303248; RRID:AB_1860491; RRID:AB_2263126; RRID:AB_2278725; RRID:AB_476743; RRID:AB_630940; RRID: SCR_002865
资金
- JO and JR Wicking Trust (Equity Trustees)
Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of A beta neuropathology (APP(SWE)/PS1(dE9)) from 6 months of age. After 6 months of housing in standard laboratory cages, APP(SWE)/PS1(dE9) (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to A beta plaque pathology in the neocortex or hippocampus of APP(SWE)/PS1(dE9) mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APP(SWE)/PS1(dE9) mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APP(SWE)/PS1(dE9) mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with A beta deposition.
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