期刊
NEUROCHEMISTRY INTERNATIONAL
卷 63, 期 1, 页码 54-60出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2013.04.002
关键词
Prefrontal cortex; Alzheimer's disease; Novelty; Synaptophysin; c-fos; Arc
资金
- Lundbeck Foundation
- Danish Council for Strategic Research (The Programme Commission on Individuals, Disease and Society) (Cognito)
Activity-regulated cytoskeletal-associated protein (Arc) and c-Fos are immediate early gene (IEG) products induced by novelty in the hippocampus and involved in the consolidation of synaptic plasticity and long-term memory. We investigated whether induction of arc and c-fos after exposure to a novel open field environment was compromised in different neocortical areas and the hippocampal formation in APP/PS1 Delta E9 transgenic mice characterized by pronounced accumulation and deposition of beta amyloid (A beta). Notably, the basal level of Arc and c-fos mRNA in the neocortex was significantly lower in APP/PS1 Delta E9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1 Delta E9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels in APP/PS1 Delta E9 as in the wild-type mice. In contrast, synaptophysin levels did not differ between mutant and wild type mice, suggesting that the observed effect was not due to a general decrease in the number of presynapses. These data suggest a reduction in basal and novelty-induced neuronal activity in a transgenic mouse model of Alzheimer's disease, which is most pronounced in cortical regions, indicating that a decreased functional response in IEG expression could be partly responsible for the cognitive deficits observed in patients with Alzheimer's disease. (c) 2013 Elsevier Ltd. All rights reserved.
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