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Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling
Authors:Yimin Jiang  Yunshi Lin  Yuhang Tan  Xinkai Shen  Meihua Liao  Huan Wang  Nannan Lu  Feng Han  Nenggui Xu  Chunzhi Tang  Juxian Song  Rongrong Tao
Affiliation:1. South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, China;2. College of Life Science and Technology, Dalian University, Dalian, China;3. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA;4. Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China
Abstract:

Aims

Cerebrovascular impairment contributes to the pathogenesis of Alzheimer's disease (AD). However, it still lacks effective intervention in clinical practice. Here, we investigated the efficacy of electroacupuncture (EA) in cerebrovascular repair in 3xTg-AD mice and its mechanism.

Methods

3xTg-AD mice were employed to evaluate the protective effect of EA at ST36 acupoint (EAST36). Behavioral tests were performed to assess neurological disorders. Laser speckle contrast imaging, immunostaining, and Western blot were applied to determine EAST36-boosted cerebrovascular repair. The mechanism was explored in 3xTg mice and endothelial cell cultures by melatonin signaling modulation.

Results

EAST36 at 20/100 Hz effectively alleviated the olfactory impairment and anxiety behavior and boosted cerebrovascular repair in AD mice. EAST36 attenuated cerebral microvascular degeneration in AD mice by modulating endothelial cell viability and injury. Consequently, the Aβ deposits and neural damage in AD mice were reversed after EAST36. Mechanistically, we revealed that EAST36 restored melatonin levels in AD mice. Melatonin supplement mimicked the EAST36 effect on cerebrovascular protection in AD mice and endothelial cell cultures. Importantly, blockage of melatonin signaling by antagonist blunted EAST36-induced cerebrovascular recovery and subsequent neurological improvement.

Conclusions

These findings provided strong evidence to support EAST36 as a potential nonpharmacological therapy against cerebrovascular impairment in AD. Further study is necessary to better understand how EAST36 treatment drives melatonin signaling.
Keywords:Alzheimer's disease  cerebrovascular impairment  electroacupuncture at ST36 acupoint  endothelial cell  melatonin signaling
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