Effect of normobaric hyperoxia on behavioral deficits and neuropathology in Alzheimer's disease mouse model

Amyloid plaques in the brains are the pathological hallmark of Alzheimer's disease (AD). Amyloid-β (Aβ), the central component of amyloid plaques, is generated from amyloid-β protein precursor (AβPP), following β- and γ-secretase cleavage. The molecular mechanism underlying the pathogenesis of AD is still unknown and there has been no effective treatment for AD. Clinical data showed that brain cerebral perfusion of most AD patients was reduced before memory and cognitive impairment incurred. Hypoxia is the direct consequence of hypoperfusion. Improving oxygen supply in the brain might exert potential effective influence on AD pathology. Normobaric hyperoxia (NBO), in addition to serving as a tool for enhancement of oxygen delivery, was protective in recent experimental and clinical pilot studies as well. In the present study, we evaluated the potential neuroprotective effects of NBO on behavioral deficits and neuropathology in AD. Morris water maze tests showed that NBO treatment notably improved the spatial learning and memory deficits in AβPP/PS1 transgenic mice. Immunohistochemical and thioflavin S staining showed that NBO treatment significantly decreased Aβ deposition and neuritic plaques formation in the cortex and hippocampus of AβPP/PS1 transgenic mice. Immunoblotting and ELISA assay revealed that NBO treatment reduced Aβ production by inhibiting γ-secretase cleavage of AβPP. Our study suggests that NBO may have a potential therapeutic effect at the early stage of AD.