Orexin A peptidergic system: Comparative physiology, morphology and population between brains of nomal and Alzheimer’s disease mice

Abstract Sleep disturbance is common in patients with Alzheimer’s disease (AD), and orexin A is a pivotal neurotransmitter for bidirectional regulating the amyloid-β (Aβ) deposition of AD brain and poor sleep. In the present study, we examined the characteristic of sleep-wake architecture in APPswe/PSldE9 (APP/PS1) and Aβ-treated mice using electroencephalogram (EEG) and electromyographic (EMG) analysis. We compared the expression of orexin A, distribution, and morphology of the corresponding orexin A neurons using innovative methods including three-dimensional reconstruction and brain tissue clearing between Wild type (WT) and APP/PS1 mice. Results from our study demonstrated that increased wakefulness and reduced NREM sleep were seen in APP/PS1 and Aβ treated mice while the expression of orexin A was significantly upregulated. Higher density and distribution of orexin A activated neurons were seen in APP/PS1 mice, with a location of 1.06 mm to 2.30 mm away from the anterior fontanelle compared to 1.34 mm to 2.18 mm away from the anterior fontanelle in WT mice. These results suggested that the population and distribution of orexin A may play an important role in the progression of AD.