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 ◽  
...  

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.

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jing Jiang ◽  
Ning Ding ◽  
Kang Wang ◽  
Zhigang Li

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.


2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Xunhu Gu ◽  
Hanjun Wu ◽  
Yuqin Xie ◽  
Lijun Xu ◽  
Xu Liu ◽  
...  

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.


Author(s):  
Narges Marefati ◽  
Amin Mokhtari-Zaer ◽  
Farimah Beheshti ◽  
Sareh Karimi ◽  
Zahra Mahdian ◽  
...  

Abstract Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 – p < 0.001). However, treatment with both doses of estradiol (20 and 60 μg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 – p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 – p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.


2020 ◽  
Author(s):  
Kazunori Sasaki ◽  
Noelia Geribaldi-Doldan ◽  
Qingqing Wu ◽  
Julie Davies ◽  
Francis G. Szele ◽  
...  

Abstract Background Much attention has recently focused on nutraceuticals which are widely used to promote health. In particular, nutraceuticals with minimal side effects have been developed for preventing or treating neurological diseases such as Alzheimer’s disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. Methods To test the neuroprotection of ethanol extract of Aurantiochytrium (EEA) and n-Hex layer of EEA (HEEA), amyloid-beta (Aβ)-stimulated SH-SY5Y cells was used for in vitro AD model. We then assessed the enhancement of neurogenesis of EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to SAMP8 mice, a non-transgenic strain with accelerated aging and Alzheimer’s-like memory loss for evaluation of spatial learning and memory using MWM test. Finally, we performed immunohistochemical analysis using mice brain fed with EEA for assessment of neurogenesis. Results Pre-treatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, n-Hex layer (HEEA), ameliorated Aβ-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular ATP production. Moreover, EEA treatment significantly increased the number of neurospheres, whilst HEEA treatment significantly increased the number of β-III-tubulin + young neurons and GFAP + astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. Learning ability was assessed in the Morris water maze test. EEA and HEEA decreased escape latency time in SAMP8 mice, indicating improved memory. To detect activated stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU + cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU + GFAP + stem cells as well as their progeny, BrdU + NeuN + mature neurons. Conclusions Our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against some age-related diseases including neurodegenerative desease, particularly AD.


2020 ◽  
Vol 107 (1) ◽  
pp. 30-39 ◽  
Author(s):  
S. Raman ◽  
M. Asle-Rousta ◽  
M. Rahnema

AbstractSocial isolation damages the nervous system by weakening the antioxidant system and leading to behavioral disorders. Fennel (Foeniculum vulgare Mill.) is an herbal plant that has antioxidant and neuroprotective properties. The objective of this study was to evaluate the effect of fennel methanol extract and its major component trans-anethole on spatial learning and memory, anxiety and depression in male rats exposed to social isolation stress.Rats were divided into six groups of Control (C), Fennel (F), trans-Anethole (A), Isolation, Isolation-F and Isolation-A. The rats were kept in the cage alone for 30 days to induce isolation. Fennel extract (150 mg/kg) and trans-anethole (80 mg/kg) were also gavaged during this period. At the end of the course, spatial learning and memory, anxiety and depression were measured by Morris water maze (MWM), elevated plus maze (EPM) and forced swimming test (FST), respectively.Learning and memory were impaired in isolated rats. Swimming time and distance to reach the hidden platform in these animals increased compared with controls (P < 0.05). In the EPM test, the percentage of open arm entries and open arm time also decreased significantly in the Isolation group (P < 0.01). The immobilization time in FST also increased significantly in these animals compared with the Control group (P < 0.001). Fennel and trans-anethole were both able to eliminate these changes in isolated rats.It is concluded that fennel and its major component, trans-anethole are suitable candidates for the prevention and treatment of stress-induced neurological disorders.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuan-Yuan Li ◽  
Nan-Qu Huang ◽  
Fei Feng ◽  
Ying Li ◽  
Xiu-Mei Luo ◽  
...  

Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer’s disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aβ) and β-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aβ1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aβ1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.


Author(s):  
Kazunori Sasaki ◽  
Noelia Geribaldi-Doldán ◽  
Qingqing Wu ◽  
Julie Davies ◽  
Francis G. Szele ◽  
...  

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.


2019 ◽  
Vol 32 (3) ◽  
pp. 152-163 ◽  
Author(s):  
Li Lin ◽  
Sarmad Sheraz Jadoon ◽  
Shang-Zhi Liu ◽  
Ru-Yi Zhang ◽  
Fan Li ◽  
...  

Background: Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aβ25 -35-mediated apoptosis. However, few studies try to understand how Aβ1-42 affects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level. Methods: Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aβ1-42 except the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats. Results: We observed that Aβ1-42 infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aβ1-42 also could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aβ1-42 could increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK-3β). Meanwhile, these phenomena could be ameliorated when Tan IIA was used. Conclusion: We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3β signal pathway.


Author(s):  
Asma Ulhusna Shaimi ◽  
Hasmah Abdullah ◽  
Zalina Ismail ◽  
Wan Amir Nizam Wan Ahmad

Dehydroepiandrosterone sulphate (DHEAS) is a neurosteroid that is found in greater concentration within the brain rather than in any other body organ (Corpechot et al., 1981) and studies have shown that in the brain, DHEAS has a role in enhancing both learning and memory (Markowski et.al., 2001). This present study investigated the relationship between DHEAS and spatial learning and memory in the rat hippocampus. Male Sprague-Dawley rats were divided into two groups and their spatial learning behaviour was evaluated with the Morris Water Maze. The intensity of DHEAS was simultaneously recorded in real time via the Fiber Fluorescence Microscopy (FFM) S-650 probe of the Cellvisio system. There were significant changes in the swimming pattern of the experimental groups obtained via the Morris Water Maze from day 1 until day 5 and day 6 for the probe test. Meanwhile, it was also seen that the intensity of DHEAS fluorescence increased in parallel to the swimming pattern of the experimental rats in comparison to the control group. The findings suggest that the changes in DHEAS fluorescence has a strong link to both spatial learning and memory.


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