Circadian learning and memory changes in Aβ1-42 induced Alzheimer's mice.

Abstract

Alzheimer disease (AD) is a growing health problem globally, which causes a progressive decline in learning and memory and multiple disturbances of circadian rhythms. Six Alzheimer's mice and six wild type (WT) mice were involved in this study. Morris Water Maze (MWM) tasks were conducted hourly to evaluate their circadian learning and memory performance. We used a single cosinor-based method to evaluate the circadian learning and memory of Alzheimer's mice and WT mice, respectively. An area sensor was used to record locomotor activity for 2weeks continuously, including 7days of 12h light/12h dark (LD) conditions and 7days of 12h dark/12h dark (DD) conditions. All WT mice showed circadian rhythm presence in learning and memory, and the peak of escape latency appeared at circadian time (CT) 12. Only one in six Alzheimer's mice showed a circadian rhythm, but the peak of escape latency was postponed to CT20. Alzheimer's mice showed rhythm absence under LD or DD conditions. Under LD conditions, the WT mice activity was higher than that in the Alzheimer's mice during ZT0-5 (p = 0.007) and ZT18-23 (p = 0.353) but lower during ZT6-11 (p < 0.001) and ZT12-17 (p < 0.001). Learning and memory of wild type mice is proved to have a circadian variation throughout a day. In Alzheimer's mice, rhythmic locomotor activity and circadian learning and memory performance were disrupted. Understanding the role of rhythmic disturbances in the process of AD may assist to identify therapeutic targets.