Emerging evidence suggests that sleep deprivation (SD) is a public health epidemic and increase the risk of Alzheimer's disease (AD) progression. However, the underlying mechanisms remain to be fully investigated. In this study, we investigate the impact of 72 h SD on the prefrontal cortex (PFC) of 3∼4-months-old APP/PS1 transgenic AD mice - at an age before the onset of plaque formation and memory decline. Our results reveal that SD alters delta, theta and high-gamma oscillations in the PFC, accompanied by increased levels of excitatory postsynaptic signaling (NMDAR, GluR1, and CaMKII) in AD mice. SD also caused alteration in the dendritic length and dendritic branches of PFC pyramidal neurons, accompanied by a reduction in neuroprotective agent CREB. This study suggests that failure to acquire adequate sleep could trigger an early electrophysiological, molecular, and morphological alteration in the PFC of AD mice. Therapeutic interventions that manipulate sleep by targeting these pathways may be a promising approach toward delaying the progression of this incurable disease.

新出现的证据表明，睡眠剥夺 (SD) 是一种公共卫生流行病，会增加阿尔茨海默病 (AD) 进展的风险。然而，潜在的机制仍有待充分研究。在这项研究中，我们调查了 72 小时 SD 对 3~4 个月大 APP/PS1 转基因 AD 小鼠的前额叶皮层 (PFC) 的影响 - 在斑块形成和记忆力下降之前的年龄。我们的研究结果表明，SD 改变了 PFC 中的 delta、theta 和高伽马振荡，伴随着 AD 小鼠中兴奋性突触后信号（NMDAR、GluR1 和 CaMKII）水平的增加。SD 还引起 PFC 锥体神经元的树突长度和树突分支的改变，伴随着神经保护剂 CREB ​​的减少。这项研究表明，无法获得充足的睡眠可能会引发 AD 小鼠 PFC 的早期电生理、分子和形态学改变。通过靶向这些途径来操纵睡眠的治疗干预可能是延缓这种不治之症进展的一种有前途的方法。