The Possible Roles of Autonomic Dysregulation and Sleep Problems in the Pathogenesis of an Alzheimer's Disease Mouse Model

• Main Authors: Yu-Ting Cheng, 鄭鈺庭
• Other Authors: Cheryl C.H. Yang
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/uh8f68

碩士 === 國立陽明大學 === 腦科學研究所 === 106 === Background and Aim: Alzheimer’s disease (AD), is known as associated with beta-amyloid (Abeta) accumulation. Several studies have highlighted the frequency of sleep disturbances and autonomic dysfunction in AD. However, whether they contribute to disease onset and progression are still unclear. The aim of this study was to investigate the possible role of autonomic function and sleep patterns at an early stage in the development of AD mice. Hypothesis: APP/PS1 transgenic mice had sleep problems, autonomic dysfunction and could be discriminated from wild-type mice in early stage of AD. Material and Methods: Experiment were carried out on 17 week-old male C57/BL6 mice (n=7), APP/PS1 mice (n=8), 32 week-old C57/BL6 mice (n=9) and APP/PS1 mice (n=6) mice. One week after the mice had electrodes implanted in the skulls, the 11-hour physiological signals during the light cycle were recorded wirelessly in freely moving mice. In addition, novel object recognition and water maze were used as behavioral tests to figure out the cognitive function in mice. Immunohistochemistry (IHC) of brain sections were analyzed for Abeta accumulation and glial fibrillary acidic protein (GFAP) level related to inflammation. Results: Before APP/PS1 mice had cognitive impairment (working and spatial memory), they already had significantly lower overall autonomic activity and parasympathetic activity during sleep time. Moreover, APP/PS1 mice spent more time in wakefulness and showed significantly lower delta power as an indicator of sleep depth in quiet sleep during the light period compared to the wild-type mice. There were no significant differences in physiological parameters between WT and AD group physiological parameters after cognitive impairment (working and spatial memory)in AD group. In IHC analysis, APP/PS1 mice had Abeta accumulation and higher GFAP level than the wild-type mice, but their behavioral performances showed no significant differences compared with each other. Correlation analysis reveal that spatial memory were negative correlated with the interruption during QS. Working memory were also negative correlated with the total autonomic nerve system and parasympathetic activity during AW, QS and PS. Conclusions: We find out that the APP/PS1 mice have had autonomic dysfunction and sleep problems before cognitive impairments, which in turn, may have important implications for preventive and therapeutic interventions in AD patients.