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Icariin ameliorates Memory deficits through regulating brain insulin signaling and glucose transporters in 3×Tg-AD mice

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Neural Regeneration Research 2023年第1期18卷 183-188页

作者： Fei Yan Ju Liu Mei-Xiang Chen Ying Zhang Sheng-Jiao Wei Hai Jin Jing Nie Xiao-Long Fu Jing-Shan Shi Shao-Yu Zhou Feng Jin Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical UniversityZunyiGuizhou ProvinceChina Institute of Digestive Diseases Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina

Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that Memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and Memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid-beta brain insulin signaling glucose transporter glucose uptake icariin Memory neurodegenerative disease tau hyperphosphorylation triple-transgenic Alzheimer’s disease mice

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Mettl3依赖的m^(6)A甲基化调控CD8^(+)T细胞效应分化和记忆形成

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Science Bulletin 2024年第1期69卷 82-96页

作者：郭文慧王昭张雅娇李亚书杜倩张田田胡瑾姚英鹏张家睿徐迎弟崔晓孙振游孟昊余国涛张好建杜旭光徐靖宇于舒洋 State Key Laboratory of Animal Biotech Breeding College of Biological SciencesChina Agricultural UniversityBeijing 100193China Frontier Science Center for Immunology and Metabolism Medical Research InstituteSchool of MedicineWuhan UniversityWuhan 430071China The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University Zunyi 563000China

Efficient immune responses rely on the proper differentiation of CD8^(+)T cells into effector and Memory cells.Here,we show a critical requirement of N^6-Methyladenosine(m^(6)A)methyltransferase Mettl3 during CD8^(+)T cell responses upon acute viral infection.Conditional deletion of Mettl3 in CD8^(+)T cells impairs effector expansion and terminal differentiation in an m^(6)A-dependent manner,subsequently affecting Memory formation and the secondary response of CD8^(+)T cells.Our combined RNA-seq and m^(6)AmiCLIP-seq analyses reveal that Mettl3 deficiency broadly impacts the expression of cell cycle and transcriptional regulators.Remarkably,Mettl3 binds to the Tbx21 transcript and stabilizes it,promoting effector differentiation of CD8^(+)T cells.Moreover,ectopic expression of T-bet partially restores the defects in CD8^(+)T cell differentiation in the absence of Mettl3.Thus,our study highlights the role of Mettl3 in regulating multiple target genes in an m^(6)A-dependent manner and underscores the importance of m^(6)A modification during CD8^(+)T cell response.

关键词： CD8^(+)T cell T cell response Mettl3 m^(6)A Effector Memory

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Effect of disrupted episodic Memory on food consumption:no impact of neuronal loss of endophilin A1 on food intake and energy balance

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Journal of Genetics and Genomics 2022年第4期49卷 329-337页

作者： Jacques Togo Yanrui Yang Sumei Hu Jia-Jia Liu John R.Speakman State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Shijingshan DistrictBeijing 100049China CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Institute of Biological and Environmental Sciences University of AberdeenAberdeen AB242TZUK CAS Center of Excellence for Animal Evolution and Genetics KunmingYunnan 650223China

Food intake is generally assumed to reflect a regulatory tension between homeostatic and hedonic drivers.Information from individuals with Memory dysfunction suggests that episodic Memory may also play a significant role.We reasoned that if Memory influences food intake,then disrupting a genetic factor that is important in episodic Memory formation should affect food intake and energy balance.We performed spatial learning tests on neuronal specific endophilin A1(EENA1)KO mice using the four-arm baited version of the radial arms maze(RAM).Energy regulation has also been evaluated.As anticipated neuronal EENA1 KO mice had impaired spatial Memory.However,loss of endophilin A1 did not result in greater food intake,or altered energy absorption efficiency,relative to wild-type(WT)mice,when fed either low or high fat diets.Moreover,loss of EENA1 did not significantly affect other features of energy balance—physical activity and energy expenditure.No statistically significant changes were observed in the expression of hypothalamic neuropeptides related to food intake regulation,or circulating levels of leptin.We conclude that food intake and energy balance are largely governed by homeostatic and hedonic processes,and when these processes are intact Memory probably plays a relatively minor role in food intake regulation.

关键词： Memory Food intake Endophilin A1 Obesity Energy expenditure Physical activity

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Rapid Eye Movement Sleep Consolidates Social Memory

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Neuroscience Bulletin 2023年第10期39卷 1598-1600页

作者： Jingkai Fan Fang Zhou Junqiang Zheng Han Xu Department of Neurobiology and Department of Neurology of the Second Afliated Hospital Zhejiang University School of MedicineHangzhou 310058China Liangzhu Laboratory MOE Frontier Science Center for Brain Science and Brain-Machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou 311121China NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang UniversityHangzhou 310058China Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of MedicineHangzhou City UniversityHangzhou 310015China

Social Memory is one of declarative Memory which is essential for animals to exhibit appropriate social behaviors.Evidence suggests that the hippocampus,particularly the CA2 region,plays an important role in encoding and consolidating social Memory[1].Rapid eye movement(REM)sleep has been suggested to contribute to social Memory consolidation by up-regulating synaptic plasticity,local field potentials,and dendritic activity[2].

关键词： Memory plasticity consolidation

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Enriched environment for offspring improves learning and Memory impairments induced by sevoflurane exposure during the second trimester of pregnancy

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Neural Regeneration Research 2022年第6期17卷 1293-1298页

作者： Shao-Wei Yin Yi-Lin Meng Chuang Li Yuan Wang Department of Obstetrics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Anesthesiology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Studies in animals indicate that sevoflurane exposure in the second trimester of pregnancy has harmful effects on the learning and Memory of offspring.Whether an enriched environment can reverse the damage of sevoflurane exposure in the second trimester of pregnancy on the learning and Memory of rat offspring remains unclear.In this study,rats at 14 days of pregnancy were exposed to 3.5%sevoflurane for 2 hours and their offspring were treated with an enriched environment for 20 successive days.We found that the enriched environment for offspring increased nestin and Ki67 levels in hippocampal tissue,increased hippocampal neurogenesis,inhibited glycogen synthase kinase 3βactivity,and increased the expression of cell proliferation-relatedβ-catenin and apoptosis-related Bcl-2,indicating that an enriched environment reduces sevoflurane-induced damage by increasing the proliferation of stem cells in the hippocampus.These findings suggest that an enriched environment can reverse the effects of sevoflurane inhaled by rats during the second trimester of pregnancy on learning and Memory of offspring.This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018PS07K)on January 2,2018.

关键词： apoptosis fetal learning Memory neurogenesis offspring proliferation sevoflurane signal pathway

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Stochastic gravitational wave background due to gravitational wave Memory

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Science China(Physics,Mechanics & Astronomy) 2022年第11期65卷 132-139页

作者： Zhi-Chao Zhao Zhoujian Cao Institute for Frontiers in Astronomy and Astrophysics Beijing Normal UniversityBeijing102206China Department of Astronomy Beijing Normal UniversityBeijing100875China School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou310024China

Gravitational wave Memory is an important prediction of general relativity, which has not been detected yet. Amounts of Memory events can form a stochastic gravitational wave Memory background. Here we find that Memory background can be described as a Brownian motion in the condition that the observation time is longer than the averaged time interval between two successive Memory events. We investigate, for the first time, the Memory background of binary black hole coalescences. We only consider the spectrum of the Memory background for a relatively low frequency range. So we can use the step function to approximate the waveform for each Memory event. Then we find that the spectrum is a power law with index –2. And the amplitude of the power law spectrum depends on and only on the merger rate of the binary black holes. Consequently, the Memory background not only provides a brand new means to detect gravitational wave Memory but also opens a new window to explore the event rate of binary black hole mergers and the gravity theory. Space-based detectors are ideal to detect the gravitational wave Memory background which corresponds to supermassive binary black holes. Since gravitational wave Memory is only sensitive to the merger stage of binary black hole coalescence, the Memory background will be an ideal probe of the famous final parsec problem.

关键词： gravitational wave Memory stochastic background

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The Necessary and Sufficient Conditions of Exponential Stability for Heat and Wave Equations with Memory

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Journal of Systems Science & Complexity 2024年第3期37卷 1037-1051页

作者： LI Lingfei ZHANG Xiaoyi ZHOU Xiuxiang School of Science Northeast Electric Power University School of Mathematics and Statistics Lingnan Normal University

This paper is addressed to a study of the stability of heat and wave equations with Memory.The necessary and sufficient conditions of the exponential stability are investigated by the theory of Laplace transform. The results show that the stability depends on the decay rate and the coefficient of the kernel functions of the Memory. Besides, the feedback stabilization of the heat equation is obtained by constructing finite dimensional controller according to unstable eigenvalues. This stabilizing procedure is easy to operate and can be applicable for other parabolic equations with Memory.

关键词： Memory stability stabilization

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A high-speed 2D optoelectronic in-Memory computing device with 6-bit storage and pattern recognition capabilities

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Nano Research 2022年第3期15卷 2472-2478页

作者： Jialin Meng Tianyu Wang Zhenyu He Qingxuan Li Hao Zhu Li Ji Lin Chen Qingqing Sun David Wei Zhang State Key Laboratory of ASIC and System School of MicroelectronicsFudan UniversityShanghai 200433China National Integrated Circuit Innovation Center No.825 Zhangheng RoadShanghai 201203China

The explosively developed era of big-data compels the increasing demand of nonvolatile Memory with high efficiency and excellent storage properties.Herein,we fabricated a high-speed photoelectric multilevel Memory device for neuromorphic computing.The novel two-dimensional(2D)MoSSe with a unique Janus structure was employed as the channel,and the stack of Al_(2)O_(3)/black phosphorus quantum dots(BPQDs)/Al_(2)O_(3)was adopted as the dielectric.The storage performance of the resulting Memory could be verified by the endurance and retention tests,in which the device could remain stable states of programming and erasing even after 1,000 cycles and 1,000 s.The multibit storage could be realized through both different voltage amplitudes and pulse numbers,which could achieve 6 bits(64 distinguishable levels)under pulse width of 50 ns.Furthermore,our Memory device also could realize the simulations of synapses in human brain with optical and electric modulations synergistically,such as excitatory post-synaptic current(EPSC),long-term potentiation/depression(LTP/LTD),and spike-timing-dependent plasticity(STDP).Neuromorphic computing was successfully achieved through a high recognition of handwritten digits up to 92.5%after 103 epochs.This research is a promising avenue for the future development of efficient Memory and artificial neural network systems.

关键词： Memory multibit two-dimensional(2D) MoSSe Co-modulation

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The impact of the design of learning spaces on attention and Memory from a neuroarchitectural approach:A systematic review

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Frontiers of Architectural Research 2022年第3期11卷 542-560页

作者： Mar Llorens-Gamez Juan Luis Higuera-Trujillo Carla Sentieri Omarrementeria Carmen Llinares Department of Architectural Projects Universitat Politecnica de ValenciaValencia 46022Spain Institute for Research and Innovation in Bioengineering(i3B) Universitat Politecnica de ValenciaValencia 46022Spain

Enriched environments in animal models have demonstrated that exposure to an optimal stimulus improves behavior,cognition,and genomics.However,the evidence base for the neurophysiological influence of human environment enrichment has not been extensively studied.This systematic review compiles indicators about the effect of built,indoor environments on the cognitive processes of Memory and attention in humans.This work pursues two main objectives:(1)to define current knowledge and the methods that are useful and identify whether previously published studies indicate consistencies and(2)to report the approaches and strategies that can be used in evaluating cognitive processes affected by environment response.Results of this systematic review show that(1)form and geometry,(2)space distribution and context,(3)color and texture,(4)height,width,and enclosure,(5)transition and circulation,and(6)light,sound,and temperature have an impact on Memory and/or attention,and they can be assessed objectively.Despite all the advances in this field,methodological limitations and a lack of cross-validated standard protocols are found.Therefore,future research is necessary to provide a deep insight into how human cognition can be heightened by the environment to which it is exposed.

关键词： Built environment Neuroarchitecture Cognition Attention Memory Learning spaces

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Local heroes or villains:tissue-resident Memory T cells in human health and disease

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Cellular & Molecular Immunology 2020年第2期17卷 113-122页

作者： S.C.Sasson C.L.Gordon S.N.Christo P.Klenerman L.K.Mackay Translational Gastroenterology Unit Nuffield Department of MedicineUniversity of OxfordOxfordUK Department of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Department of Infectious Diseases Austin HealthMelbourneVICAustralia Peter Medawar Building for Pathogen Research University of OxfordOxfordUK

Tissue-resident Memory T(T_(RM))cells are increasingly associated with the outcomes of health and disease.T_(RM) cells can mediate local immune protection against infections and cancer,which has led to interest in T_(RM) cells as targets for vaccination and immunotherapies.However,these cells have also been implicated in mediating detrimental pro-inflammatory responses in autoimmune skin diseases such as psoriasis,alopecia areata,and vitiligo.Here,we summarize the biology of T_(RM) cells established in animal models and in translational human studies.We review the beneficial effects of T_(RM) cells in mediating protective responses against infection and cancer and the adverse role of T_(RM) cells in driving pathology in autoimmunity.A further understanding of the breadth and mechanisms of T_(RM) cell activity is essential for the safe design of strategies that manipulate T_(RM) cells,such that protective responses can be enhanced without unwanted tissue damage,and pathogenic T_(RM) cells can be eliminated without losing local immunity.

关键词： human T cells tissue-resident Memory immunity

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