Abstract
Enriched environment exposure improves several aspects of cognitive performance in Alzheimer’s disease patients and in animal models and, although the role of amyloid plaques is questionable, several studies also assessed their response to enriched environment, with contrasting results. Here we report that rearing APPSwe/PS1L166P mice in an enriched environment since birth rescued the spatial memory impairment otherwise present at 6 months of age. At the same time, the exposure to the enriched environment caused a transient acceleration of plaque formation, while there was no effect on intracellular staining with the 6E10 antibody, which recognizes β-amyloid, full length amyloid precursor protein and its C-terminal fragments. The anticipation of plaque formation required exposure during early development, suggesting an action within critical periods for circuits formation. On the other hand, chronic neuronal activity suppression by tetrodotoxin decreased the number of plaques without affecting intracellular amyloid. These results indicate that enriched environment exposure since early life has a protective effect on cognitive deterioration although transiently accelerates amyloid deposition. In addition, the effects of the enriched environment might be due to increased neuronal activity, because plaques were reduced by suppression of electrical signaling by tetrodotoxin.
Highlights
Alzheimer’s disease (AD), a severe neurodegenerative disorder, is the most common form of dementia
The progressive formation of Ab plaques and intracellular deposits was studied in hippocampus and entorhinal cortex because they are the earliest and most severely affected areas in AD, and functional deficits in these structures are related to the first symptoms of memory impairment in AD patients [33]
Amyloid plaques were almost absent in 1-month-old APPSwe/PS1L166P and beginning from 2 months of age they showed a progressive increase until the last time point analysed of 12 months
Summary
Alzheimer’s disease (AD), a severe neurodegenerative disorder, is the most common form of dementia. Positively regulates APP processing at the b–secretase site, inducing an increase in APP-cleavage products with a consequent increase in Ab production and secretion into the interstitial fluid [21,22,23] This is in line with the observation that the areas of the human brain with the highest default activity, including the medial temporal lobe, are among the most vulnerable to early AD pathology [24]. Amyloid plaques are transiently increased, but only in mice exposed to EE in a time window that includes the critical periods of experience-dependent circuits formation and refinement We confirm that these effects may be attributed to neuronal activity, as its suppression causes a significant decrease in plaque deposition. We show that intracellular APP/Ab levels are not influenced by neuronal activity, suggesting a minor role of intracellular amyloid deposits in cognitive deterioration
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