Electroacupuncture attenuates cognition impairment via anti-neuroinflammation in an Alzheimer’s disease animal model

Abstract

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities and memory leading to dementia. Electroacupuncture (EA) is a complementary alternative medicine approach, applying an electrical current to acupuncture points. In clinical and animal studies, EA causes cognitive improvements in AD and vascular dementia. However, EA-induced changes in cognition and microglia-mediated amyloid β (Aβ) degradation have not been determined yet in AD animals. Therefore, this study investigated the EA-induced molecular mechanisms causing cognitive improvement and anti-inflammatory activity in five familial mutation (5XFAD) mice, an animal model of AD.Methods5XFAD mice were bilaterally treated with EA at the Taegye (KI3) acupoints three times per week for 2 weeks. To evaluate the effects of EA treatment on cognitive functions, novel object recognition and Y-maze tests were performed with non-Tg, 5XFAD (Tg), and EA-treated 5XFAD (Tg + KI3) mice. To examine the molecular mechanisms underlying EA effects, western blots, immunohistochemistry, and micro-positron emission tomography scans were performed. Furthermore, we studied synapse ultrastructures with transmission electron microscopy and used electrophysiology to investigate EA effects on synaptic plasticity in 5XFAD mice.ResultsEA treatment significantly improved working memory and synaptic plasticity, alleviated neuroinflammation, and reduced ultrastructural degradation of synapses via upregulation of synaptophysin and postsynaptic density-95 protein in 5XFAD mice. Furthermore, microglia-mediated Aβ deposition was reduced after EA treatment and coincided with a reduction in amyloid precursor protein.ConclusionsOur findings demonstrate that EA treatment ameliorates cognitive impairment via inhibition of synaptic degeneration and neuroinflammation in a mouse model of AD.

Effect of Combined Electroacupuncture and Selegiline Treatment in Alzheimer’s Disease: An Animal Model

“…These findings are conducive to cognitive improvements, which also align with the results of the cognitive tests performed in this study. Improved cognitive functions were also demonstrated by increased metabolic activity and lesser Aβ accumulation in 18 F-FDG scans, similar to previous findings (Jagust and Landau, 2012;Wang et al, 2012;Zhang et al, 2012;Cai et al, 2019;Jiang et al, 2019). Therefore, we suggest that SEL combined with EA treatment improved cognitive function by activation of frontal cortex with an increase in glucose metabolism.…”

Experimental Evidence of the Benefits of Acupuncture for Alzheimer's Disease: An Updated Review

“…Zhang et al ( 2013 ) reported that acupuncture prevented neuron loss and decreased the number of activated astrocytes in the hippocampal CA1 and CA3 regions of SAMP8 mice. Cai et al ( 2019 ) demonstrated that EA stimulation ameliorated cognitive impairment via inhibition of synaptic degeneration and neuroinflammation in 5xFAD mice, as evidenced by decreased expression of CD11b (for microglia) and GFAP (for astrocytes) in the prefrontal cortex. Similarly, EA was reported to attenuate microglia-mediated Aβ 1−42 deposition in the prefrontal cortex, as supported by a reduction in colocalized Aβ 1−42 and CD68 (a microglia marker).…”

“…Enhanced glucose metabolic activity in the hippocampus, thalamus, hypothalamus, and frontal/temporal lobes, accompanied by restored memory, following acupuncture treatment was observed in SAMP8 mice (Lai et al, 2016 ). Using microPET, 2 Hz EA stimulation was shown to increase glucose metabolism in the frontal cortex and hypothalamus in 5xFAD mice (Cai et al, 2019 ). In summary, these findings suggest that enhancement of glucose metabolism in cognition-related brain regions could be an important mechanism of the beneficial effects of acupuncture in AD.…”

Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

“…The activated astrocytes and microglia could generate various proin ammatory factors like interleukin-6 (IL -6) and interleukin-1 beta (IL-1β), which increased the deposition of Aβ and the levels of amyloid beta precursor protein (APP) in AD models [5]. Microglia mainly participate in the process of neuroin ammatory, and its phagocytosis on surround hyperphosphorylated Tau aggregates and amyloid plaques restrain AD development [6]. Therefore, anti-in ammation has been presented as a potential therapeutic strategy in AD.…”