Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling

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.

Visualization of Microcirculation at Acupoints in vivo of Alzheimer’s Disease Animal Model with Photoacoustic Microscope: A Pilot Study

“…Furthermore, animal experiments have demonstrated that the ST36 acupoint could enhance the cognitive functions and slow down the progression of the central nervous system in animal models of AD. This was achieved through the activation of various signaling pathways such as TLR4/NF kB [ 44, 45 ], JNK [ 46 ], melatonin [ 47 ], RhoA/ROCK [ 48 ], and P38 [ 49 ], with a particular emphasis on restoring the balance of gut microbiota [ 46, 50, 51 ]. Simultaneously, our team has discovered, via several prior experimental investigations, that acupuncture could enhance the cognitive functions of SAMP8 mice by rectifying the dysbiosis of gut microbiota [ 52 ].…”

A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer’s disease based on the neuroinflammatory

“…This treatment approach also resulted in the decreased levels of APP, its C-terminal fragment (CTFs), and Aβ deposits, and inhibited glial cell activation in the prefrontal cortex and hippocampus of 5xFAD. Yu et al [ 176 ] and Yimin Jiang et al [ 178 ] assessed the improvement effect of acupuncture at different frequencies on AD mice, and they found that high-frequency EA exhibited promising results, effectively inhibiting the activity of GSK-3β in the presence of Aβ1-42. This inhibition led to a reduction in learning and memory impairments induced by Aβ1-42 and provided protection against damage to synaptic ultrastructure.…”