Disrupted prefrontal neuronal oscillations and morphology induced by sleep deprivation in young APP/PS1 transgenic AD...

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.