Electroacupuncture Improves Cognitive Function in Senescence-Accelerated P8 (SAMP8) Mice via the NLRP3/Caspase-1 Pathway

Abstract

Background. Clinically, electroacupuncture (EA) is the most common therapy for aging-related cognitive impairment (CI). However, the underlying pathomechanism remains unidentified. The aims of this study were to observe the effect of EA on cognitive function and explore the potential mechanism by which EA acts on the NLRP3/caspase-1 signaling pathway. Main Methods. Thirty male SAMP8 mice were randomly divided into the model, the 2 Hz EA and 10 Hz EA groups. Ten male SAMR1 mice were assigned to the control group. Cognitive function was assessed through the Morris water maze test. Hippocampal morphology and cell death were observed by HE and TUNEL staining, respectively. The serum IL-1β, IL-6, IL-18, and TNF-α levels were measured by ELISA. Hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1β, IL-18, Aβ, and tau proteins were detected by Western blotting. Key Findings. Cognitive function, hippocampal morphology, and TUNEL-positive cell counts were improved by both EA frequencies. The serum IL-1β, IL-6, IL-18, and TNF-α levels were decreased by EA treatment. However, 10 Hz EA reduced the number of TUNEL-positive cells in the CA1 region and serum IL-1β and IL-6 levels more effectively than 2 Hz EA. NLRP3/caspase-1 pathway-related proteins were significantly downregulated by EA, but 2 Hz EA did not effectively reduce ASC protein expression. Interestingly, both EA frequencies failed to reduce the expression of Aβ and tau proteins. Significance. The effects of 10 Hz EA at the GV20 and ST36 acupoints on the NLRP3/caspase-1 signaling pathway may be a mechanism by which this treatment relieves aging-related CI in mice.

Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice

“…Previous studies have found that EA can effectively reduce the OxA level of insomnia patients after stroke [15]. In this study, we administered 10 Hz EA for 14 days, a treatment strategy that was previously confirmed to be efficacious [19], and found that 10 Hz EA effectively reduced the OxA level in the CSF of 7-month-old SAMP8 mice within 24 h. The spontaneous alternation rate in the Y maze test and 11 Oxidative Medicine and Cellular Longevity the percentage of time spent in the target quadrant in the MWM probe test were increased, and the latency to find the hidden platform in the MWM test was decreased, indicating that the impairment of working memory and longterm spatial memory was effectively alleviated in SAMP8 mice. These results are similar to those of previous reports showing that direct injection of OX1R antagonists into the hippocampus can relieve social learning and memory impairment caused by acute stress in rats [34].…”

“…The operation method of electroacupuncture is based on the method adopted by similar high-level research [17,18], combined with our previous studies [15,19] and preliminary experimental exploration of this research, and finally established the most suitable method for this study. The details are as follows: for EA, 0:18 × 13 mm stainless steel needles (Guizhou And Medical Appliances Ltd., Guizhou, China) were inserted at the GV20 and bilateral ST36 acupoints.…”

Electroacupuncture ameliorates neuroinflammation in animal models

“…Activated caspase-1 also promotes inflammation through cell pyroptosis. 96 Hou et al 97 suggested that EA could improve cognitive function and reduce neuroinflammation in mice by inhibiting the NLRP3/caspase-1 pathway. Sha et al 98 also found that the level of miR-223 was up-regulated after EA, which could inhibit the activity of NLRP3 by binding to the conserved site of the 3′ untranslated region (UTR), thus improving neuroinflammation and nerve injury after ischemic stroke.…”

Electroacupuncture Improves Clearance of Amyloid-β through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer’s Disease

“…EA has been shown to improve cognitive performance, neuropsychiatric symptoms, and the ability to perform daily activities in Alzheimer's patients [14,15]. Previous experimental studies have shown that EA can improve cognitive deficits in animal models of AD [16,17], and such benefit might contribute to reducing Aβ deposition and thereby delaying the pathological progression of AD from multiple pathways. For instance, EA intervention might upregulate the content of Aβ-degrading enzymes such as neprilysin (NEP) and insulin-degrading enzyme (IDE) in the brain, enhance the phagocytosis of Aβ by microglia, and improve the expression of Aβ-related transporters on the blood-brain barrier [18][19][20][21].…”

“…Here, we investigated the effect of EA on the clearance of Aβ via the glymphatic system in AD model mice, to provide more scientific experimental support for the treatment of AD with electroacupuncture. In the light of a previous study [16,20,22,23], senescence-accelerated mouse prone 8 (SAMP8) mice were used for the animal model of AD and the age-matched senescence accelerated mouse resistant 1 (SAMR1) mice as the control with normal aging phenotype. After EA treatment, the Morris water maze (MWM) test was applied to evaluate cognition, HE and Nissl staining to determine brain histomorphology, ELISA to ascertain the expression of Aβ, contrast-enhanced MRI for the assessment of glymphatic system function, and immunofluorescence to assess the reactivity of astrocytes and AQP4 polarization.…”