IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2022
·
IF 3.712
Hairui Zhou,Jingru Wu,Yu Gong,Zilong Zhou,Jingtao Wang
Purpose: Sleep deprivation (SD) leads to memory and cognitive impairment due to damage to the hippocampus. Isoquercetin possesses neuron-protective properties. Our study aimed to investigate the effects of isoquercetin on SD-induced hippocampal neurons damage and the underlying mechanism.Materials and methods: Herein, the cognitive competence was evaluated by Morris water maze test after SD. The morphology of the hippocampus was observed after Nissl staining. Moreover, the level of NLRP3 was detected by Immunofluorescent staining and western blot. In vitro study, pyroptosis was tested by TUNEL assay and flow cytometry. The levels of pyroptosis-related factors were measured by western blot.Results: The results indicated that isoquercetin improved spatial memory and prevented change of hippocampal neurons of SD mice. Moreover, SD upregulated NLRP3 level, which was downregulated by isoquercetin. Additionally, isoquercetin rescued the increase of pyroptosis and the upregulation of NLRP3, caspase-1, ASC, IL-1β, IL-18, and GSDMD levels induced by LPS.Conclusions: In conclusion, isoquercetin improved learning and cognitive capability of SD mice via suppressing NLRP3-induced pyroptosis of hippocampal neurons cells, suggesting that isoquercetin might be an efficacious drug for memory disorders caused by SD.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
·
2024
·
IF 4.6
Weng Jiyu,Wang Ying,Tan Zekai,Yuan Yanghe,Huang Shiyuan,Li Zexi,Li Yiming,Zhang Lanyue,Du Zhiyun
Objectives Chronic neuroinflammation has become one of the important causes of common neurodegeneration disease. Therefore, the target of this study was to explore the protective action of glabridin on lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro and its mechanism. Methods The neuroinflammation model was established by LPS-induced BV2 cells. The cell viability with various concentrations of glabridin was determined by MTT assay, and the content of NO in each group was detected. A neuroinflammatory model was established in male C57BL/6J mice for a water maze test. Subsequently, NF-κB and SOD indices were measured by ELISA, GFAP and IBA-1 indices were measured by immunofluorescence, and Nissl staining was used to explore the Nissl bodies in the hippocampus of mice. Results In vitro experiments, our results expressed that glabridin could markedly increase the cell activity of LPS-induced BV2 cells and reduce the NO expression in cells. It indicated that glabridin had a remarkable impact on the neuroinflammation of LPS-induced BV2 cell protection. In vivo neuroinflammation experiments, mice treated with different doses of glabridin showed significantly improved ability of memory compared with the LPS group in the Morris water maze test. The levels of NF-κB, GFAP, and the number of positive cells in Nissl staining were decreased. High-dose glabridin significantly increased the SOD content in the brain tissue and decreased the IBA-1 levels. Conclusion Glabridin can significantly reduce or even reverse LPS-induced neuroinflammation, which may be related to the fact that glabridin can reduce the NO expression, NF-κB, IBA-1, GFAP, and other inflammatory mediators, upregulate the expression of SOD to relieve oxidative stress of brain and inhibit the activation of gliocyte in brain tissue.
研究领域:
神经科学
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药理学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2020
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IF 3.171
Jian-Zhu Bo,Ling Xue,Shuang Li,Jing-Wen Yin,Zheng-Yao Li,Xi Wang,Jun-Feng Wang,Yan-Shu Zhang
Although exogenous D-serine has been applied as a neural regulatory intervention in many studies, the role played by D-serine in hippocampal injuries caused by lead exposure remains poorly understood. Rat models of chronic lead exposure were established through the administration of 0.05% lead acetate for 8 weeks. Simultaneously, rats were administered 30 or 60 mg/kg D-serine, intraperitoneally, twice a day. Our results showed that D-serine treatment shortened the escape latency from the Morris water maze, increased the number of times that mice crossed the original platform location, and alleviated the pathological damage experienced by hippocampal neurons in response to lead exposure. Although D-serine administration did not increase the expression levels of the N-methyl-D-aspartate receptor subtype 2B (NR2B) in the hippocampi of lead-exposed rats, 60 mg/kg D-serine treatment restored the expression levels of NR2A, which are reduced by lead exposure. These findings suggested that D-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of NR2A in the hippocampus. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China (approval No. LX2018155) on December 21, 2018.
研究领域:
神经科学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2017
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IF 3.883
Jing Sun,Wenjie Xie,Xufeng Zhu,Mengmeng Xu,Jie Liu
Functionalized nanomaterials, which have been applied widely to inhibit amyloid-β protein (Aβ) aggregation, show enormous potential in the field of prevention and treatment of Alzheimer’s disease (AD). A significant body of data has demonstrated that the morphology and size of nanomaterials have remarkable effects on their biological behaviors. In this work, we proposed and designed three kinds of brain-targeting sulfur nanoparticles (RVG@Met@SNPs) with novel morphologies (volute-like, tadpole-like, and sphere-like) and investigated the effect of different RVG@Met@SNPs on Aβ–Cu2+ complex aggregation and their corresponding neurotoxicity. Among them, the sphere-like nanoparticles (RVG@Met@SS) exhibited the most effective inhibitory activity, due to their unique mini size effect, and they reduced 61.6% the Aβ–Cu2+ complex aggregation and increased 92.4% SH-SY5Y cell viability in a dose of 10 μg/mL. In vitro and in vivo, the abilities of different morphologies of RVG@Met@SNPs to cross the blood–brain barrier (BBB) and target brain parenchymal cells were significantly different. Moreover, improvements in learning disability and cognitive loss were shown in the transgenic AD mice model using the Morris water maze test after multiple doses of RVG@Met@SNPs treatment. In general, the purpose of this research is to develop a biological application of sulfur nanoparticles and to provide a novel functionalized nanomaterial to treat AD.
研究领域:
纳米技术
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神经科学
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药学科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
NEUROIMMUNOMODULATION
·
2021
·Vol. 29
·期 1
·63-69
·
IF 2.492
Liu Hong,Zhong Lili,Dai Qiaomei,Yang Jing,Zhang Yuwei,Zhang Bo,Jiang Ying
Introduction: Alzheimer’s disease is the most popular neurodegenerative disorder with no effective drugs to stop the progression. Zuoguiwan (ZGW), a traditional Chinese herbal medicine, has been applied in many diseases. Our study aimed to detect the function and mechanisms of ZGW in Alzheimer’s disease (AD). Methods: The rat models of AD were established by streptozotocin (STZ), and the function of ZGW on cognitive dysfunction was measured with the Morris water maze test. The concentration of pro-inflammatory mediators was accessed by enzyme-linked immunosorbent assay. The relative mRNA expression of ERβ was detected by real-time quantitative PCR. Results: The treatment with ZGW could suppress the cognitive impairment by the findings of escape latency and time spent in the target quadrant and the increased concentration of IL-1β, IL-6, and TNF-α induced by STZ. STZ might repress the mRNA levels of ERβ, and ZGW management weakened the declined mRNA expression of ERβ. ZGW might play a protective role in AD rats against the injury of STZ on cognition and neuro-inflammation by improving the mRNA expression of ERβ. Conclusion: The results indicated that ZGW might be a novel therapeutic strategy to slow the process of AD by modulating ERβ
研究领域:
神经科学
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药理学
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中医
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2023
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IF 5
Mo-li Zhu,Jie Zhang,Li-juan Guo,Rui-zhu Yue,Shan-shan Li,Bao-yue Cui,Shuang Guo,Qian-qian Niu,Ya-nan Yu,Huan-huan Wang,Lin Yang,Ya-ling Yin,Shuang-xi Wang,He-qin Zhan,Zhi-tao Gao,Peng Li
Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze , Transcranial Doppler TCD, hematoxylin–eosin (HE) staining , Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NEUROTOXICITY RESEARCH
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2021
·Vol. 39
·期 6
·1800-1811
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IF 3.911
Zhou Wei,Hu Mengmeng,Hu Jingrong,Du Zhiyun,Su Qing,Xiang Zhangmin
Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae , is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.
研究领域:
神经科学
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药理学
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免疫学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
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2017
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IF 1.424
Jimei Bu,Hengbing Zu
Objective(s): In previous studies, researchers observed that doxepin could improve cognitive processes and has protective effects on the central nervous system. Thus, this study was designed to analyze the effects of doxepin on β-amyloid (Aβ)-induced memory impairment and neuronal toxicity in rat and to explore the underlying mechanism. Materials and Methods: Rats were treated with Aβ1-42 and doxepin was injected to validate its effects on cognitive function. The Morris water maze test was performed to detect memory function. Aβ1-42-treated SH-SY5Y human neuroblastoma cell line was also used to detect the effects of doxepin and to explore the underlying mechanism. Western blotting analysis was used to detect the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. Results: After treated with 1 mg/kg of doxepin, Aβ1-42-treated rats showed markedly lower escape latency and higher platform-finding strategy score. Low doses of doxepin significantly reversed the effects of Aβ1-42 on the protein expression levels of PSD-95, synapsin 1, p-AKT and p-mTOR in rats. In vitro experiment showed the consistent results. Besides, PI3K inhibitor (LY294002) treatment could markedly reversed the effects of doxepin on Aβ1-42-treated SH-SY5Y cells. Conclusion: Our results demonstrated that doxepin could protect against the Aβ1-42-induced memory impairment in rats. The protective effect of doxepin was associated with the enhancement of PSD-95 and synapsin 1 expression via PI3K/AKT/mTOR signaling pathway.
研究领域:
神经科学
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药理学
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认知科学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
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2024
·
IF 2.7
Zhu Wang,Bowen Li,Jingrui Yang,Ying Gao,Liu Gao,Qiang Jia,Li Yu,Yunzhi Ling
The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1β expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1β expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus.
研究领域:
神经科学
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药理学
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外科手术
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炎症
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认知障碍
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROREPORT
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2024
·
IF 1.6
Bian Jing,Liu Chunxu,Li Xiang,Qin Xiaoye,Wang Feng,Xuan Lina,Zhang Weimin
This study aims to investigate how electroacupuncture regulates the learning and memory abilities of poststroke cognitive impairment (PSCI) rats through the TLR4/NF-κB/NLRP3 signaling pathway on the hippocampal microglia. Thirty male rats were randomly divided into three groups: sham surgery group, PSCI model group, and electroacupuncture group, with 10 rats in each group. Middle cerebral artery occlusion was used to establish the PSCI model. The Zea Longa method was used to score the rats’ neurological function. Electroacupuncture was utilized for 21 days to improve PSCI. The learning and memory abilities of rats were tested using the Morris water maze. Hematoxylin–eosin staining and immunofluorescence were used to find the hippocampus’ pathological changes. The concentration of interleukin-1β, interleukin-6, tumor necrosis factor-α, and interleukin-18 were detected by ELISA. The mRNA expression levels of associated inflammatory corpuscles were measured by quantitative real-time PCR. The protein expression levels of TLR4, MyD88, NF-κB, and NLRP3 were measured using western blotting. Electroacupuncture improved not only the learning and memory abilities of PSCI rats but also hippocampal morphology. Electroacupuncture inhibited the activation of microglia and the TLR4/NF-κB/NLRP3 signaling pathway. Electroacupuncture also reduced proinflammatory factors and restrained the mRNA levels of NLRP3-associated inflammatory cytokines. Its mechanism was related to inhibiting the expression of the TLR4/NF-κB/NLRP3 signaling pathway, attenuating the release of inflammatory factors, and regulating the activation of hippocampal microglia in the brain.
研究领域:
神经科学
·
针灸
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认知障碍
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
Neuropsychiatric Disease and Treatment
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2022
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IF 2.989
Ting Zhang,Keli Dong,Lan Xiao,Guangcheng Li,Zhanwei Zhang
Objective We investigated the effect of icariin (ICA) combined with Panax notoginseng saponins (PNS) on intestinal microbiota and hippocampal protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, a model of Alzheimer’s disease (AD).Methods Transgenic mice were treated with icariin and PNS. The Morris water maze (MWM) was used to assess spatial memory, and the gut microbiota and differential protein expression in the hippocampus were investigated using high-throughput screening techniques. Differential protein expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.Results The MWM results showed that the mice treated with the medium dose of ICA+PNS spent significantly more time in the target quadrant compared with the AD group. Bacterial diversity was the lowest in the AD group, with significantly greater diversity in the ICA + PNS treatment group. Three proteins were selected for proteomic analysis, and qRT-PCR and Western blot were used to detect the expression of 2ʹ-5ʹ-oligoadenylate synthetase ubiquitin like 1 (Oasl1), trichoplein keratin filament-binding protein (TCHP), and tumor necrosis factor receptor associated 3-interacting protein 1 (MIPT3). Compared with control mice, MIPT3 expression was increased and Oasl1 and TCHP were reduced in the AD group. These abnormal protein expressions tended to normalization after treatment with medium dose of ICA and PNS.Conclusion Treatment with ICA and PNS ameliorated memory impairment in an AD mouse model. The mechanisms may be related to modulation of the intestinal microbiota and expression of Oasl1, TCHP, and MIPT3.
研究领域:
神经科学
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药理学
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微生物学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2024
·Vol. 14
·期 4
·327
·
IF 2.7
Yuhan Wu,Hui Hu,Weiwei Liu,Yun Zhao,Fang Xie,Zhaowei Sun,Ling Zhang,Huafeng Dong,Xue Wang,Lingjia Qian
Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into the mouse’s hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders.
研究领域:
神经科学
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认知科学
·
分子生物学
·
表观遗传学
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产品关联
DOI
PubMed
高影响因子
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