scholarly journals Electroacupuncture Could Influence the Expression of IL-1β and NLRP3 Inflammasome in Hippocampus of Alzheimer’s Disease Animal Model

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Jiang ◽  
Ning Ding ◽  
Kang Wang ◽  
Zhigang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Nlrp3 Inflammasome ◽  
Day Treatment ◽  
Control Group ◽  
Acupuncture Points ◽  
Spatial Learning And Memory ◽  
Caspase 1 ◽  
Samp8 Mice

Background. Effective therapies for Alzheimer’s disease (AD) are still being explored. Electroacupuncture with traditional Chinese medicine theory may improve spatial learning and memory abilities and glucose metabolism rates in an animal model of AD. However, the mechanism of electroacupuncture in intervention of AD is still unclear. According to recent studies of AD mechanisms, the NLRP3 inflammasome regulated the expression of IL-1β in the brain which may mediate AD related processes. Therefore, in our study, we intend to explore the possible relation between electroacupuncture and the expression of NLRP 3 inflammasome in the hippocampus of an AD animal model. Method. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an AD animal model, which were randomly divided into two groups: Alzheimer’s disease model group (AD group) and electroacupuncture group (EA group). In the control paradigm, 7.5-month-old male SAMR1 mice were used as the normal control group (N group). DU20, DU26, and EX-HN3 were selected as the acupuncture points, and after a 15-day treatment of electroacupuncture, we used immunohistochemistry and Western blotting to examine the expression of IL-1β and NLRP3, ASC, and Caspase-1 in the hippocampus of the AD animal model. Results. Compared with N group, IL-1β, NLRP3, ASC, and Caspase-1 positive cells in AD group were increased, and the relative expression of all above proteins significantly increased (P < 0.01). Compared with AD group, the expression of IL-1β, NLRP3, ASC, and Caspase-1 in EA group was significantly decreased (P < 0.01). Conclusion. Electroacupuncture treatment could inhibit the inflammation reaction in the hippocampus of SAMP8 mice. What is more, the possible mechanism of electroacupuncture reduced the expression of IL-1β and NLRP3 inflammasome relative protein.

scholarly journals Manual Acupuncture Suppresses the Expression of Proinflammatory Proteins Associated with the NLRP3 Inflammasome in the Hippocampus of SAMP8 Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ning Ding ◽  
Jing Jiang ◽  
Menghan Lu ◽  
Jiatong Hu ◽  
Yiyuan Xu ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Nlrp3 Inflammasome ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Manual Acupuncture ◽  
Caspase 1 ◽  
Donepezil Hydrochloride ◽  
Related Proteins ◽  
Samp8 Mice

Objective. To investigate the effect of manual acupuncture (MA) on NLRP3 inflammasome-related proteins. Methods. SAMP8 mice were randomly divided into Alzheimer’s disease (AD) group, the MA group, and the medicine (M) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 μg/g. In the MA group, MA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26). The Morris water maze was applied to assess spatial learning and memory. Immunohistochemical staining and western blot analysis were used to observe the expression of NLRP3 inflammasome-related proteins. Results. Compared with the normal (N) control group, spatial learning and the memory capabilities of the AD group significantly decreased (p<0.01). The number of NLRP3, ASC, Caspase-1, and IL-1β positively stained cells in the AD group was higher than the N group, and the relative expression levels of the above proteins were significantly higher than those in the N group (p<0.01). These changes were reversed by both MA and donepezil (p<0.01). Conclusion. MA can improve the learning and memory capabilities of SAMP8 mice. The negative regulation of the NLRP3/Caspase-1 pathway in the hippocampus may be a possible mechanism of MA in the treatment of AD.

scholarly journals Caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1 in Alzheimer’s disease

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Xunhu Gu ◽  
Hanjun Wu ◽  
Yuqin Xie ◽  
Lijun Xu ◽  
Xu Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Membrane Transport ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Senile Plaque ◽  
Spatial Learning And Memory ◽  
Memory Ability ◽  
Caspase 1 ◽  
Plaque Deposition

Abstract Background Alzheimer's disease is a neurodegenerative disease. Previous study has reported that caspase-1/IL-1β is closely associated with Alzheimer's disease. However, the biological role of caspase-1/IL-1β in Alzheimer's disease has not been fully elucidated. This study aimed to explore the mechanism of action of caspase-1/IL-1β in Alzheimer's disease. Methods Mouse hippocampal neurones were treated with Aβ1-42 to induce Alzheimer's disease cell model. APP/PS1 mice and Aβ1-42-induced hippocampal neurones were treated with AC-YVAD-CMK (caspase-1 inhibitor). Spatial learning and memory ability of mice were detected by morris water maze. Flow cytometry, TUNEL staining, Thioflavin S staining and immunohistochemistry were performed to examine apoptosis and senile plaque deposition. Enzyme linked immunosorbent assay and western blot were performed to assess the levels of protein or cytokines. Co-Immunoprecipitation was performed to verify the interaction between Stargazin and GluA1. Results AC-YVAD-CMK treatment improved spatial learning and memory ability and reduced senile plaque deposition of APP/PS1 mice. Moreover, AC-YVAD-CMK promoted membrane transport of GluA1 in APP/PS1 mice. In vitro, Aβ1-42-induced hippocampal neurones exhibited an increase in apoptosis and a decrease in the membrane transport of GluA1, which was abolished by AC-YVAD-CMK treatment. In addition, Stargazin interacted with GluA1, which was repressed by caspase-1. Caspase-1/IL-1β inhibited membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1. Conclusions Our data demonstrate that caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin in Alzheimer's disease. Thus, caspase-1/IL-1β may be a target for Alzheimer's disease treatment.

scholarly journals Toll-Like Receptor 2 and NLRP3 Cooperate To Recognize a Functional Bacterial Amyloid, Curli

2014 ◽  
Vol 83 (2) ◽  
pp. 693-701 ◽  
Author(s):  
Glenn J. Rapsinski ◽  
Meghan A. Wynosky-Dolfi ◽  
Gertrude O. Oppong ◽  
Sarah A. Tursi ◽  
R. Paul Wilson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nlrp3 Inflammasome ◽  
Amyloid Β ◽  
Underlying Mechanism ◽  
Secondary Amyloidosis ◽  
Toll Like Receptor ◽  
Content Type ◽  
Caspase 1 ◽  
Toll Like Receptor 2

Amyloids are proteins with cross-β-sheet structure that contribute to pathology and inflammation in complex human diseases, including Alzheimer's disease, Parkinson's disease, type II diabetes, and secondary amyloidosis. Bacteria also produce amyloids as a component of their extracellular matrix during biofilm formation. Recently, several human amyloids were shown to activate the NLRP3 inflammasome, leading to the activation of caspase 1 and production of interleukin 1β (IL-1β). In this study, we investigated the activation of the NLRP3 inflammasome by bacterial amyloids using curli fibers, produced bySalmonella entericaserovar Typhimurium andEscherichia coli. Here, we show that curli fibers activate the NLRP3 inflammasome, leading to the production of IL-1β via caspase 1 activation. Investigation of the underlying mechanism revealed that activation of Toll-like receptor 2 (TLR2) by curli fibers is critical in the generation of IL-1β. Interestingly, activation of the NLRP3 inflammasome by curli fibers or by amyloid β of Alzheimer's disease does not cause cell death in macrophages. Overall, these data identify a cross talk between TLR2 and NLRP3 in response to the bacterial amyloid curli and generation of IL-1β as a product of this interaction.

scholarly journals The Neuroprotective Effect of Byu d Mar 25 in LPS-Induced Alzheimer's Disease Mice Model

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lan Liu ◽  
Yongcang Zhang ◽  
Liang Tang ◽  
Hua Zhong ◽  
Dunzhu Danzeng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Inflammatory Factors ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Expression Levels ◽  
Caspase 1 ◽  
Tnf Α

Inflammatory factors play an important role in the pathogenesis of Alzheimer’s disease (AD). Byu d Mar 25 (BM25) has been suggested to have protective effects in the central nervous system. However, the effect of BM25 on AD has not been determined. This study aims to investigate the neuroprotective effect of BM25 in AD. A total of 40 AD model mice were randomly assigned to the following five groups (n = 8 per group): the AD + NS group, the AD + donepezil group, and three AD + BM25 groups treated with either 58.39 mg/kg (AD + BM25-L), 116.77 mg/kg (AD + BM25-M), or 233.54 mg/kg BM25 (AD + BM25-H). The Morris water maze test was performed to assess alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuronal damage. The expression of IL-1β and TNF-α was evaluated by ELISA. The protein expression of P-P38, P38, P-IκBα, caspase 1, COX2, and iNOS was determined by western blotting. The expression of Aβ, p-Tau, and CD11b was measured by immunohistochemistry. The mRNA expression levels of IL-1β, TNF-α, COX2, and iNOS were measured by qRT-PCR. Spatial memory significantly improved in the AD + BM25-M and AD + BM25-H groups compared with the AD + NS group ( p < 0.05 ). The expression of Aβ and p-Tau significantly decreased in the AD + BM25-M and AD + BM25-H groups ( p < 0.05 ). The neuron density and hierarchy and number of pyramidal neurons significantly increased in the AD + BM25-M and AD + BM25-H groups ( p < 0.05 ). In addition, the expression levels of CD11b, IL-1β, TNF-α, COX2, iNOS, caspase 1, p-IκBα, and p-P38 significantly decreased in the AD + BM25-M and AD + BM25-H groups ( p < 0.05 ). In conclusion, our findings suggest that BM25 may exert anti-inflammatory and neuroprotective effects in AD model mice by suppressing the activity of microglia and inhibiting the phosphorylation of IκBα and p38 MAPK.

scholarly journals A UPLC-Q-TOF/MS-Based Metabolomics Study on the Effect of Corallodiscus flabellatus (Craib) B. L. Burtt Extract on Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yang-Yang Wang ◽  
Ning Zhou ◽  
Yan-Po Si ◽  
Zhi-Yao Bai ◽  
Meng Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolite Profiling ◽  
Huperzine A ◽  
Control Group ◽  
Model Group ◽  
Metabolomics Study ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse ◽  
Tof Ms

A UPLC-Q-TOF/MS-based metabolomics study was carried out to explore the intervening mechanism of Corallodiscus flabellatus (Craib) B. L. Burtt (CF) extract on Alzheimer’s disease (AD). The AD model group consisted of senescence-accelerated mouse prone 8 (SAMP8) mice, and the control group consisted of senescence-accelerated mouse resistant 1 (SAMR1) mice. UPLC-Q-TOF/MS detection, multivariate statistical analysis, and pathway enrichment were jointly performed to research the change in metabolite profiling in the urine of AD mice. The result suggested that the metabolite profiling of SAMP8 mice significantly changed at the sixth month compared with SAMR1 mice of the same age, and the principal component analysis (PCA) score scatter plots of the CF group closely resembled those of the control and positive drug (huperzine A, HA) group. A total of 28 metabolites were considered potential biomarkers associated with the metabolism of beta-alanine, glycine, serine, threonine, cysteine, methionine, arginine, proline, and purines in AD mice. Furthermore, the CF group was clustered with the control and positive group and was clearly separated from the model group in the heat map. In conclusion, significant anti-AD effects were firstly observed in mice after treatment with the CF extract, and the urinary metabolomics approach assisted with dissecting the underlying mechanism.

scholarly journals Electroacupuncture could balance the gut microbiota and improve the learning and memory abilities of Alzheimer’s disease animal model

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259530
Author(s):  
Jing Jiang ◽  
Hao Liu ◽  
Zidong Wang ◽  
Huiling Tian ◽  
Shun Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Gut Microbiota ◽  
Learning And Memory ◽  
Amplicon Sequencing ◽  
Tnf Α ◽  
16S Rdna Amplicon Sequencing ◽  
Nerve System ◽  
Samp8 Mice

Alzheimer’s disease (AD), as one of most common dementia, mainly affects older people from the worldwide. In this study, we intended to explore the possible mechanism of improving cognitive function and protecting the neuron effect by electroacupuncture. Method: We applied senescence-accelerated mouse prone 8 (SAMP8) mice as AD animal model, used Morris water maze, HE staining, 16S rDNA amplicon sequencing of gut microbiota and ELISA to demonstrate our hypothesis. Results: electroacupuncture improved the learning and memory abilities in SAMP8 mice (P<0.05) and could protect the frontal lobe cortex and hippocampus of SAMP8 mice; electroacupuncture significantly decreased the expression of IL-1β (P<0.01), IL-6 (P<0.01) and TNF-α (P<0.01 in hippocampus, P<0.05 in serum) in serum and hippocampus; electroacupuncture balanced the quantity and composition of gut microbiome, especially of the relative abundance in Delta-proteobacteria (P<0.05) and Epsilon-proteobacteria (P<0.05). Conclusion: electroacupuncture treatment could inhibit the peripheral and central nerve system inflammatory response by balancing the gut microbiota.

scholarly journals Pharmacological and Epigenetic Regulators of NLRP3 Inflammasome Activation in Alzheimer’s Disease

2021 ◽  
Vol 14 (11) ◽  
pp. 1187
Author(s):  
Francesca La Rosa ◽  
Roberta Mancuso ◽  
Simone Agostini ◽  
Federica Piancone ◽  
Ivana Marventano ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nlrp3 Inflammasome ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Protein Translation ◽  
Inflammasome Activation ◽  
Peripheral Blood Mononuclear ◽  
Caspase 1 ◽  
Inflammatory Status

Activation of the NLRP3 inflammasome complex results in the production of IL-18, Caspase-1 and IL-1β. These cytokines have a beneficial role in promoting inflammation, but an excessive activation of the inflammasome and the consequent constitutive inflammatory status is a negative factor in human pathologies including Alzheimer’s Disease (AD). MicroRNAs (miR-NAs) target the 3′UTR region of NLRP3, preventing the activation of the inflammasome and inhibiting cytokine production. Because Stavudine (D4T), an antiretroviral drug, was recently shown to reduce inflammasome activation, we verified whether its effect is mediated by miR-7-5p, miR-22-3p, miR-30e-5p and miR-223-3p: miRNAs that bind the NLRP3-mRNA-UTR region and interfere with protein translation, reducing NLRP3 activation. Peripheral blood mononuclear cells (PBMCs) of twenty AD patients and ten sex-matched Healthy Controls (HC) were stimulated with Lipopolysaccharides (LPS)+Amyloid-beta (Aβ42) in the absence/presence of D4T. Expression of genes within the inflammasome complex and of miRNAs was evaluated by RT-PCR; cytokines and caspase-1 production was measured by ELISA. Results have shown that: NLRP3, ASC, IL-1β and IL-18 expression, as well as IL-18, IL-1β and caspase-1 production, were significantly augmented (p < 0.05) in LPS+Aβ42-stimulated PBMCs of AD patients compared to HC. D4T reduced the expression of inflammasome genes and cytokine production (p < 0.005). miR-7-5p and miR-223-3p expression was significantly increased in LPS+Aβ42-stimulated PBMCs of AD patients (p < 0.05), and it was reduced by D4T in AD alone. In conclusion: miR-223-3p and mir-7-5p expression is increased in AD, but this does not result in down-regulation of NLRP3 inflammasome expression and of IL-1β and IL-18 production. D4T increased miRNA expression in HC but had an opposite effect in AD, suggesting that miRNA regulatory mechanisms are altered in AD.

scholarly journals Effects of manual acupuncture combined with donepezil in a mouse model of Alzheimer’s disease

2019 ◽  
Vol 37 (1) ◽  
pp. 64-71
Author(s):  
Jing Jiang ◽  
Gang Liu ◽  
Suhua Shi ◽  
Yujie Li ◽  
Zhigang Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Combined Therapy ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Manual Acupuncture ◽  
Male Mice ◽  
Model Of Alzheimer’S Disease ◽  
Aβ Amyloid

Objectives: To explore whether combined therapy with donepezil and acupuncture is better than treatment with donepezil or acupuncture individually in a rat model of Alzheimer’s disease. Methods: In this study, we randomly divided 40 7.5-month-old senescence-accelerated mouse prone 8 (SAMP8) male mice into four groups: SAMP8, SAMP8+D, SAMP8+MA and SAMP8+D+MA. An additional 10 7.5-month-old SAMR1 male mice were included as a healthy control group (SAMR1). Mice in the SAMP8+D group were given donepezil at a dose of 0.65 µg/g/day; mice in the SAMP8+MA group underwent manual acupuncture at GV20, GV26 and Yintang for 20 min per day; mice in the SAMP8+D+MA received both donepezil and manual acupuncture; and mice in the SAMR1 and SAMP8 groups underwent restraint only to control for the effects of handling. After the 15-day treatment, the Morris water maze test, micro-PET(positron-emission tomography), H&E (haematoxylin and eosin) staining, and immunohistochemistry were used to study the differences between donepezil (SAMP8+D), acupuncture (SAMP8+MA), and donepezil combined with acupuncture (SAMP8+D+MA) therapy for the treatment of Alzheimer’s disease. Results: We found that, compared with the untreated SAMP8 group, donepezil, manual acupuncture, and combined therapy with donepezil and manual acupuncture all improved spatial learning and memory ability, the level of glucose metabolism in the brain, and the content of Aβ amyloid in the cortex. Moreover, combined therapy outperformed treatment with donepezil or acupuncture individually in the SAMP8 mice. Conclusion: This study shows that the combination of manual acupuncture and donepezil in an Alzheimer’s disease animal model is superior to acupuncture and donezepil alone. However, randomised controlled trials should be undertaken to clarify the clinical efficacy of combination therapy.

Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 842-843
Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Paired Helical Filaments ◽  
Ethanol Intoxication ◽  
Drg Neurons ◽  
Critical Difference ◽  
Suitable Animal Model ◽  
The Central Nervous System ◽  
Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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