Low-intensity pulsed ultrasound enhances delivery of 30 nm Q10 for improving mental and memory disorder in APP/PS1 mice.

Abstract

Patients with Alzheimer's disease (AD) often experience mental and memory disorders with poor outcomes. Coenzyme Q10 can degrade formaldehyde (FA) and improve Alzheimer-related symptoms, but its ability to cross the blood-brain barrier (BBB) is limited. This study investigated whether low-intensity pulsed ultrasound (LIPUS) enhances 30 nm Q10 delivery and improve symptoms in AD model mice. Here, 30 nm Q10 was prepared by encapsulating Q10 in liposomes coupled with PEG, creating PEG-Q10@NPs under 30 nm in diameter. Wild-type mice and APPswe/PS1dE9 mice (a familial AD model) received 30 nm Q10 via intraperitoneal injection, or a combination of 30 nm Q10 and LIPUS (50 or 100 100 mW/cm²). Then the mice's anxiety-like and depression-like behaviors and biochemical index were evaluated. We found that the combination therapy of LIPUS at 100 mW/cm² and 30 nm Q10 was more effective in ameliorating psychosis in AD mice than individual treatments with 30 nm Q10. This effectiveness was linked to higher levels of brain Q10, serotonin (5-HT), and dopamine (DA), along with lower levels of FA and plaques. Especially, excessive FA directly inactivated 5-HT and DA in vitro. The enhanced cellular uptake of Q10 and improved BBB permeability facilitated by LIPUS were confirmed in both cultured cells and wild-type mice. Unexpectedly, LIPUS at the different intensity only partially alleviated anxiety and depression symptoms and memory deficits in AD mice. Hence, this combination therapy of LIPUS and 30 nm Q10 is an innovative strategy for ameliorating mental and cognitive disorders in AD.