Electroacupuncture at ST 36 ameliorates cognitive impairment and beta-amyloid pathology by inhibiting NLRP3 inflammasome activation in an Alzheimer's disease animal model

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder leading to cognitive impairment in the elderly, and no effective treatment exists. Increasing evidence has demonstrated that physical therapy and electroacupuncture (EA) effectively improve spatial learning and memory abilities. Nevertheless, the mechanism underlying the effects of EA on AD pathology is largely unexplored. Acupuncture at Zusanli (ST 36) has previously been shown to improve cognitive impairment in AD, but the mechanism is unclear. According to recent studies, EA drives the vagal-adrenal axis from the hindlimb ST 36 acupoint but not from the abdominal Tianshu (ST 25) to curb severe inflammation in mice. This study examined whether ST 36 acupuncture improves cognitive dysfunction in AD model mice by improving neuroinflammation and its underlying mechanism.Methods: Male 5xFAD mice (aged 3, 6, and 9 months) were used as the AD animal model and were randomly divided into three groups: the AD model group (AD group), the electroacupuncture at ST 36 acupoint group (EA-ST 36 group), and the electroacupuncture at ST 25 acupoint group (EA-ST 25 group). Age-matched wild-type mice were used as the normal control (WT) group. EA (10 Hz, 0.5 mA) was applied to the acupoints on both sides for 15 min, 5 times per week for 4 weeks. Motor ability and cognitive ability were assessed by the open field test, the novel object recog-nition task, and the Morris water maze test. Thioflavin S staining and immunofluorescence were used to mark A & beta; plaques and microglia. The levels of NLRP3, caspase-1, ASC, interleukin (IL)-1 & beta;, and IL-18 in the hippocampus were assayed by Western blotting or qRT-PCR.Results: EA at ST 36, but not ST 25, significantly improved motor function and cognitive ability and reduced both A & beta; deposition and microglia and NLRP3 inflammasome activation in 5xFAD mice.Conclusion: EA stimulation at ST 36 effectively improved memory impairment in 5xFAD mice by a mechanism that regulated microglia activation and alleviated neuroinflammation by inhibiting the NLRP3 inflammatory response in the hippocampus. This study shows that ST 36 may be a specific acupoint to improve the condition of AD patients.

Automated summary

This study investigated the mechanism of electroacupuncture in improving cognitive dysfunction in Alzheimer's disease (AD) model mice. The results showed that electroacupuncture at the Zusanli (ST 36) acupoint significantly improved motor and cognitive abilities in 5xFAD mice, and reduced amyloid-beta deposition, microglia activation, and NLRP3 inflammasome activation. This study suggests that ST 36 may be a specific acupoint for improving the condition of AD patients.