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Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo., Methods: Senescence-accelerated mouse prone 8 (SAMP8) mice were used as AD models and received EA at Yingxiang (LI 20, bilateral) and Yintang (GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin (2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier (BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid- β (Aβ), and ionized calcium-binding adapter molecule 1 (IBa-1) in mouse hippocampus (CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining. Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining., Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8 mice and this was inhibited by EA treatment (P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice (P<0.01), which was reversed by fibrin injection (P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability (P<0.05 or P<0.01). Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8 mice, which was reversed by fibrin injection (P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1 (HMGB1)/toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE)/nicotinamide adenine dinucleotide phosphate (NADPH) signaling pathways (P<0.01)., Conclusion: EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Synaptic dysfunction and neuronal loss are related to cognitive impairment of Alzheimer's disease. Recent evidence indicates that regulating the phosphatidylinositol 3-Kinase (PI3K)/AKT/GSK-3β pathway is a therapeutic strategy for improving synaptic plasticity in Alzheimer's disease. Here, we investigated "olfactory three-needle" effects on synaptic function and the PI3K/AKT/GSK-3β signaling pathway in β-amyloid 1-42 (Aβ 1-42 )-induced Alzheimer's disease rats. A three-needle olfactory bulb insertion for 28 days alleviated Aβ 1-42 -induced Alzheimer's disease rats' cognitive impairment as assessed by performance in the Morris water maze test. Furthermore, the three-needle electrode inhibited neuro-apoptosis and neuro-inflammation. It significantly upregulated the protein expression of postsynaptic density protein 95, synaptophysin, and GAP43, indicating a protective effect on hippocampal synaptic plasticity. Additionally, the activation level of PI3K/AKT signaling and the phosphorylation inactivation of GSK-3β were significantly enhanced by the "olfactory three-needle". Our findings suggested that the three-needle acupuncture is a potential alternative to improve synaptic plasticity and neuronal survival of Alzheimer's disease brain in rodents., Competing Interests: The authors declare no competing interests., (© 2021 The Authors. Published by IMR Press.)

Objective: To explore the effect of "Xiusanzhen" [electroacupuncture (EA) of bilateral "Yingxiang" (LI 20) and "Yintang" (EX-HN 3)] on activities of hippocampal muscarinic cholinergic receptor (mAChR) and the involved neural path in Alzheimer Disease(AD)rats., Methods: Forty Sprague Dawley rats were randomly divided into normal control, model, olfactory nerve severing (ONS)-EA of "Xiusanzhen" (ONS-EA) and EA of "Xiusanzhen" (EA) groups. AD model was established by intra-hippocampal injection (AP: 3.5 mm, L:2 mm, H: -2.8 mm) of Abeta(1-40) starch-like peptide (10 microg/2 microL) under the aid of a microsyringe installed in a brain stereotaxis instrument. For rats of the ONS-EA group, the olfactory nerve was severed by using a surgical knife after drilling a hole on the skull (5 mm anterior to the bregma, L, R: 2 mm). The mAChR density, and its maximum binding capacity (Bmax) and dissociation constant (Kd) of the hippocampus tissue were measured by using radio-ligand binding analysis and Lowry's microamount protein assay., Results: In comparison with the normal control group, the hippocampal mAChR density and its Bmax in the model group were decreased remarkably (P < 0.05), while the Kd of M-receptor in the model group was increased remarkably (P < 0.05). In comparison with the model group, hippocampal mAChR density and its Bmax in the EA group were up-regulated obviously (P < 0.05), while the Kd of mAChR in the EA group was down-regulated significantly (P < 0.05). No significant differences were found between the model and ONS-EA groups in mAChR density and its Bmax and Kd (P > 0.05)., Conclusion: "Xiusanzhen"-EA can effectively up-regulate hippocampal mAChR density and Bmax and down-regulate Kd of M-receptor of hippocampus in AD rats, which is dependent on the intact olfactory nerve pathway.

Objective: To observe the effect of electroacupuncture (EA) of "Xiusanzhen" [3 acupoints, i.e., bilateral "Yingxiang" (LI 20) and "Yintang" (EX-HN 3)] on expression of B-cell lymphoma/leukemia-2 (Bcl-2, an antiapoptosis protein) and Bax (a protein for promoting apoptosis) in the hippocampus in Alzheimer disease (AD) rats, so as to explore its clinical mechanisms underlying relieving AD., Methods: A total of 40 Sprague Dawley rats were randomly divided into normal control, AD model, EA and olfactory nerve transaction(ONT) + EA groups, with 10 rats in each. AD model was established by injection of beta-amyloid (Abeta)(1-40) (2 microL containing 10 microg) into the hippocampus (Bregma: 3.5 mm, L: 2.0 mm, H: -2.8 mm below dura), and the ON was sectioned by using a fine needle. EA (80-100 Hz, 1-3 mA) was applied to bilateral LI 20 and EX-HN 3 for 10 min, once daily (except Saturdays and Sundays) for 6 weeks. The expression of Bcl-2 and Bax of hippocampus was measured by immunohisto-chemistry., Results: Compared with the normal control group, the expression of Bcl-2 of hippocampus was significantly lower in the AD model group (P<0.05), and that of Bax in AD model group was much higher (P<0.01). In comparison with the model group, the expression of hippocampal Bcl-2 was up-regulated significantly (P<0.01), and that of hippocampal Bax protein downregulated considerably in the EA group (P<0.01). No significant differences were found between AD model and ONT + EA groups in the expression of hippocampal Bcl-2 and Bax proteins (P>0.05), suggesting a necessary premise condition for EA in regulating hippocampal Bcl-2 and Bax expression., Conclusion: "Xiusanzhen" can regulate the expression of hippocampal Bcl-2 and Bax proteins in AD rats, which may contribute to its clinical effect in relieving AD, and the therapeutic effect depends on the integrity of the olfactory nerve pathway.

Objective: To probe into the therapeutic effect of perfume stimulating olfaction with volatile oil of Acorus Gramineus on the Alzheimer's disease (AD) rat., Methods: Totally 50 adult SD rats, male,weighing 300 +/- 10 g, were randomly divided into 5 groups, normal group (group A), olfactory nerve severing model group (group B), AD model group (group C), AD model plus perfume stimulation group (group D), AD model olfactory nerve severing plus perfume stimulation group (group E), 10 rats in each group. After perfume stimulation, Morris maze test was conducted for valuating the learning and memory ability; Malondaldehyde (MDA) content, and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the brain, and the brain weight were detected., Results: Compared with the AD model group, the average escape latency and swimming distance in 6 days were significantly shorter than those in the group A, B, D (P < 0.01), with no significant differences between the group C and the group E (P > 0.05); Compared with the group A, B and D, MDA content in the group C significantly increased (P < 0.01), and SOD and GSH-Px activities significantly decreased (P < 0.01), and brain weight/body weight decreased significantly in the group C (P < 0.01), with no significant differences between the group C and the group E (P > 0.05)., Conclusion: Perfume stimultating olfaction with volatile oil of Acorus Gramineus can significantly increase the learning-memory ability, decrease MDA content and increase SOD and GSH-Px activities and weight of brain in AD rats.

Objective: To explore the effect of "Xiusanzhen" [bilateral "Yingxiang" (LI 20) + "Yintang" (EX-HN 3)] on learning-memory ability and choline acetyl transferase (ChAT) and acetyl cholinesterase (AChE) activity of hippocampus tissue in Alzheimer Disease (AD) rats., Methods: A total of 40 Sprague Dawley rats were randomly divided into control, AD model, AD + olfactory-bulb lesion (OBL, induced by electrocoagulation method) + EA and "Xiusanzhen" (AD + EA) groups. AD model was established by 4-vessel occlusion. Morris water maze tests were conducted for evaluating the rat's learning-memory ability. The activity of ChAT and AChE of hippocampus tissue was detected by colorimetric method., Results: In comparison with control group, the average escape latency (AEL) prolonged significantly and the target-platform crossing times decreased remarkably in AD model group (P<0.01). In comparison with AD model group, the AEL shortened and the target-platform crossing times increased remarkably in AD + EA group (P<0.01). No significant differences were found between AD model and AD + OBL + EA groups in AEL and the target-platform crossing times (P>0.05). The ChAT and AChE activity of hippocampus in AD model group was significantly lower than that of control group (P<0.05), while that of ChAT and AChE in AD + EA group was significantly higher than that in AD model group (P<0.05). No significant difference was found between AD model and AD + OBL + EA groups in ChAT and AChE activity of hippocampus (P>0.05)., Conclusion: EA of "Xiusanzhen" can markedly raise the learning-memory ability in AD rats, which may be related to its effect in increasing the ChAT and AChE activity of hippocampus in AD rats. Its therapeutical effect also depends on the intact of the olfactory pathway.