Electroacupuncture ameliorates blood-brain barrier dysfunction in 5XFAD Alzheimer’s animal model

Abstract

Alzheimer’s disease (AD) is an irreversible and progressive neurodegenerative disease accompanied by aging, followed by memory impairment and cognitive decline. Although numerous attempts have been made to develop treatments for AD, most clinical trials have failed to delay or stop the progression of AD. Electroacupuncture (EA) is a complementary alternative medicine technique widely used to treat pain, inflammation, and neurodegenerative diseases. Additionally, blood-brain barrier (BBB) disruption is a known pathophysiology of neurodegenerative diseases, including AD. Moreover, amyloid beta deposition increases BBB permeability and produces inflammatory cytokines induced by glial activation. However, our previous study revealed that EA treatment at the Taegye acupoints (KI3) improves memory impairment through anti-neuroinflammation and increases glucose metabolism in 5XFAD mice. Therefore, we evaluated whether EA treatment at KI3 regulates BBB dysfunction in the prefrontal cortex of 5XFAD mice. For this study, 6.5-month-old 5XFAD mice were treated with EA stimulation at KI3 three times a week for two weeks. Western blotting, immunohistochemistry, and flow cytometry were used to evaluate the effects of EA treatment on BBB dysfunction. We found that EA stimulation attenuates BBB integrity by protecting BBB tight junction proteins (CD31, aquaporin 4, occludin, and claudin 5) in the prefrontal cortex of 5XFAD mice. In addition, EA treatment regulated inflammatory cytokines (IL-1α, IL-1β, IL-17, IL-23, IFN-ɣ, monocyte chemoattractant protein 1 (MCP-1), granulocyte-macrophage colony stimulating factors [GM-CSF], and IL-10) in the peripheral circulation of 5XFAD mice. Therefore, our data suggest that EA treatment could be a therapeutic agent for enhancing BBB dysfunction in AD.