Regulation of Sleep Behavior by Overexpression of Amyloid Precursor Protein in Drosophila Neurons
Regulation of Sleep Behavior by Overexpression of Amyloid Precursor Protein in Drosophila Neurons
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DOI：
10.1007/s12204-021-2261-0
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发表时间：
2021-01
影响因子：
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通讯作者：
Minzhe Li;Y. Ping
中科院分区：
文献类型：
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作者：
Minzhe Li;Y. Ping
淀粉样前体蛋白（Amyloid precursor protein，APP）可通过蛋白水解作用产生神经毒性的β-淀粉样蛋白42（β-amyloid 42，Aβ42），在阿尔茨海默病（Alzheimer's disease，AD）的发病机制中起重要作用。患有轻度至中度AD的个体甚至在AD发作之前就表现出睡眠障碍。本研究的目的是利用APP过表达的果蝇AD模型验证APP对睡眠行为的影响。APP过度表达的果蝇按年龄分组，并监测它们的睡眠量。我们的结果表明，APP过表达对幼蝇（羽化后4-7天，4-7AE）的睡眠量没有影响。然而，APP过表达导致中年（11- 14 AE）果蝇的白天和总睡眠量减少。此外，过度表达APP的老年（40 AE）果蝇表现出睡眠次数增加和睡眠时间减少，表明这些果蝇的睡眠片段化。本研究结果提示，APP在神经元中的过表达对不同年龄的睡眠行为有不同的影响，但APP调节睡眠的具体机制还需进一步研究。此外，我们的数据还表明，AD动物的睡眠障碍可能是由APP表达改变引起的，这为AD患者的睡眠干预和治疗提供了一个潜在的治疗靶点。
Amyloid precursor protein (APP) can generate neurotoxicβ-amyloid 42 (Aβ42) by proteolytic process, which plays a crucial role in the pathogenesis of Alzheimer’s disease (AD). Individuals with mild to moderate AD exhibit sleep disturbance, even before the onset of AD. The purpose of this study is to verify the effect of APP on sleep behavior by using an APP overexpressingDrosophilaAD model. APP-overexpressed flies were grouped by age, and their sleep amounts were monitored. Our results demonstrated that APP overexpression had no impacts on sleep amounts in young (4–7 days after eclosion, 4–7AE) flies. However, APP overexpression contributed to lower day and total sleep amounts in the middle-aged (11–14AE) flies. Moreover, old-aged (40AE) flies with overexpressing APP exhibited increased number of sleep bouts and decreased sleep time, indicating sleep fragmentation in these flies. Our results indicated that overexpression of APP in neurons has distinct effects on sleep behavior at different ages, but the specific mechanisms underlying the sleep regulation by APP are needed for further study. In addition, our data also suggest that sleep disturbance in AD animals can be caused by APP expression alterations, which provide a potential treating target for sleep intervention and therapy for AD patients.