期刊
NEUROBIOLOGY OF AGING
卷 108, 期 -, 页码 58-71出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2021.08.004
关键词
Mice; Touchscreen; APP; PS1; Visual discrimination; Extinction; Rodent; Executive function
资金
- Australian Government Research Training Program Scholarship
- Yulgilbar top-up scholarship
- Australian Research Council (ARC) [FT100100835, LP160100126]
- NHMRC-ARC Dementia Research Development Fellowship
- Melbourne Research Fel-lowship
- Guelma-Alaexander fellowship in Neuroscience
- Australian Research Council [FT100100835, LP160100126] Funding Source: Australian Research Council
This study is the first to characterize rewarded executive function in APP/PS1 mice, revealing different deficits in reversal and extinction tasks in mice of different ages. The results suggest that age plays a significant role in the emergence of these cognitive deficits.
Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1 Delta E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13 or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic. (c) 2021 Elsevier Inc. All rights reserved.
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