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Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

Neural Regeneration Research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun Guangxi Key Laboratory of Brain and cognitive Neuroscience Guilin Medical University department of Genetic Disease Research Osaka Metropolitan University Graduate School of Medicine department of Scientific Research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,respectively.Previous works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s disease.Despite intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent phenotypes.Interestingly,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical manifestations.Furthermore,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in vivo.On the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent manner.These findings indicate strong cross-talk between the two proteins in physiology and pathology.In this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

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Photonic neuromorphic architecture for tens-of-task lifelong learning

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Light(Science & Applications) 2024年第3期13卷 519-530页

作者： Yuan Cheng Jianing Zhang Tiankuang Zhou Yuyan Wang Zhihao Xu Xiaoyun Yuan Lu Fang Sigma Laboratory Department of Electronic EngineeringTsinghua UniversityBeijing 100084China Beijing National Research Center for Information Science and Technology(BNRist) Beijing 100084China Institute for Brain and cognitive Science Tsinghua University(THUIBCS)Beijing 100084China

Scalable,high-capacity,and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks.Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls,hindering them from the sustainable performance improvement and iterative multi-task learning.Referring to another modality of light,photonic computing has been progressively applied in high-efficient neuromorphic systems.Here,we innovate a reconfigurable lifelong-learning optical neural network(L2 ONN),for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware codesign.Benefiting from the inherent sparsity and parallelism in massive photonic connections,L2 ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field,while incrementally acquiring expertise on various tasks by gradually enlarging the activation.The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths.Extensive evaluations on freespace and on-chip architectures confirm that for the first time,L2 ONN avoided the catastrophic forgetting issue of photonic computing,owning versatile skills on challenging tens-of-tasks(vision classification,voice recognition,medical diagnosis,etc.)with a single model.Particularly,L2 ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks,and 14×larger capacity than existing optical neural networks while maintaining competitive performance on each individual task.The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme,permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

关键词： life neural versatile

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Neuron-to-astrocyte proteostatic stress signaling in response to tau pathology

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Neural Regeneration Research 2024年第3期19卷 505-506页

作者： Kevin Llewelyn Batenburg Wiep Scheper Amsterdam UMC location Vrije Universiteit Amsterdam Department of Human GeneticsAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands department of Functional Genomics Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdam Neuroscience-NeurodegenerationAmsterdamThe Netherlands

Maintenance of protein homeostasis or“proteostasis”is essential for the functioning and viability of cells.This is in particular the case for cells like neurons that cannot self-renew and acquire unique functional properties during their lifetime.Cellular proteostatic stress responses are in place to protect cells from damage in case of proteostatic challenges.The integrated stress response(ISR)is one of the key proteostatic stress responses in the cell(Costa-Mattioli and Walter,2020).The ISR is the downstream convergence point for the four stress-induced eIF2αkinases(EIF2AK1-4)that control stress-regulated protein translation via phosphorylation of the translation factor eIF2α.ISR activation results in a transient reduction of global translation while it concomitantly enhances the translation of specific mRNAs,including that encoding the activating transcription factor 4(ATF4).Together,the translational control mediated by the ISR results in a temporary reduction of the overall protein load and the selectively increased expression of proteins that contribute to restoration of the proteostatic balance.

关键词： translation stress Together

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Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

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Neural Regeneration Research 2024年第5期19卷 1133-1141页

作者： Baicheng Zhao Hang Zhang Ying Liu Gaoyu Zu Yuxiao Zhang Jiayi Hu Shuai Liu Linya You department of Human Anatomy&Histoembryology School of Basic Medical SciencesFudan UniversityShanghaiChina Shanghai Key Laboratory of Brain Functional Genomics(Ministry of Education) Affiliated Mental Health Center(ECNU)School of Psychology and Cognitive ScienceEast China Normal UniversityShanghaiChina Shanghai Changning Mental Health Center ShanghaiChina NYU-ECNU Institute of Brain and cognitive Science at NYU Shanghai ShanghaiChina Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai ShanghaiChina

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

关键词： behavioral test Brpf1 CAMKIIa-Cre intellectual disability miniature excitatory postsynaptic current mRNA-Seq

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan Zhao Yongchun Wang Mingxi Li Li Sun department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeuti

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque

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Neuroscience Bulletin 2024年第2期40卷 171-181页

作者： Lin Yang Min Jin Cong Zhang Ning Qian Mingsha Zhang Key Laboratory of cognitive Neuroscience and Learning Division of PsychologyBeijing Normal UniversityBeijing 100875China Institute of Neuroscience Key Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China department of Neuroscience and Zuckerman Institute Columbia UniversityNew York 10027USA

Even though retinal images of objects change their locations following each eye movement,we perceive a stable and continuous world.One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information.There have been several proposals on how this may be done,including eye-position modulation(gain fields)of retinotopic receptive fields(RFs)and craniotopic RFs.In the present study,we investigated coordinate systems used by RFs in the lateral intraparietal(LIP)cortex and frontal eye fields(FEF)and compared the two areas.We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation.The same recording and analysis procedures were applied to the two brain areas.We found that,in both areas,RFs were distributed from retinotopic to craniotopic representations.There was no significant difference between the distributions in the LIP and FEF.Only a small fraction of neurons was fully craniotopic,whereas most neurons were between the retinotopic and craniotopic representations.The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts.These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF,and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.

关键词： Reference frames Eye-centered Headcentered Visual stability

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Temporal Unfolding of Racial Ingroup Bias in Neural Responses to Perceived Dynamic Pain in Others

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Neuroscience Bulletin 2024年第2期40卷 157-170页

作者： Chenyu Pang Yuqing Zhou Shihui Han School of Psychological and cognitive Sciences PKU-IDG/McGovern Institute for Brain ResearchBeijing Key Laboratory of Behavior and Mental HealthPeking UniversityBeijing 100081China CAS Key Laboratory of Behavioral Science Institute of PsychologyChinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China

In this study,we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions.We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful(or non-painful)stimulation to Asian and White models’faces to trigger painful(or neutral)expressions.We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms–200 ms,in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms–200 ms,in the anterior cingulate cortex around 250 ms–350 ms,and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset.Perceived dynamic pain in White models modulated activities in the visual,anterior cingulate,and primary sensory cortices after 500 ms.Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race(vs other-race)individuals in dynamic painful situations.

关键词： Empathy Race Magnetoencephalography Dynamic pain Cingulate cortex

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Transient receptor potential vanilloid 1 involved in the analgesic effects of total flavonoids extracted from Longxuejie(Resina Dracaenae Cochinchinensis)

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Journal of Traditional Chinese Medicine 2024年第3期44卷 437-447页

作者： MO Xiaoqiang CHEN Yating YIN Qian CHEN Haibo BAN Qiang LI Jun CHEN Su YAO Jinguang department of Stomatology Affiliated Hospital of Youjiang Medical University for Nationalities College of General Practitioners Youjiang Medical University for Nationalities College of Biomedical Engineering South-Central Minzu UniversityKey Laboratory of Cognitive Science of State Ethnic Affairs CommissionHubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis and Treatment College of Pharmacy South-Central Minzu University

OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB.RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/L.TFDB(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats.CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.

关键词： Freund's adjuvant Longxuejie () capsaicin flavonoids formaldehyde inflammatory pain transient receptor potential vanilloid 1

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Foeniculum vulgare Mill.inhibits lipopolysaccharide-induced microglia activation and ameliorates neuroinflammation-mediated behavioral deficits in mice

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Asian Pacific Journal of Tropical Biomedicine 2024年第1期14卷 28-39页

作者： Sushruta Koppula Ramesh Alluri Spandana Rajendra Kopalli College of Biomedical and Health Sciences Konkuk UniversityChungju-SiChungcheongbuk Do27478Republic of Korea cognitive Science Research Initiative Lab Department of PharmacologyVishnu Institute of Pharmaceutical Education and ResearchNarsapurTelangana502313India department of Bioscience and Biotechnology Sejong UniversityGwangjin-guSeoul 05006Republic of Korea

Objective:To investigate the effect of Foeniculum vulgare extract against lipopolysaccharide(LPS)-induced microglial activation in vitro as well as cognitive behavioral deficits in mice.Methods:LPS-activated BV-2 cell viability was measured using MTT assay and reactive oxygen species(ROS)was studied using DCF-DA assay.The antioxidative enzymes and pro-inflammatory mediators were analyzed using respective ELISA kits and Western blotting.For in vivo testing,LPS(1 mg/kg,i.p.)was given daily for five days in male Swiss albino mice to produce chronic neuroinflammation.cognitive and behavioral tests were performed using open-field,passive avoidance,and rotarod experiments in LPS-induced mice.Results:Foeniculum vulgare extract(25,50 and 100μg/mL)significantly attenuated the LPS-activated increase in nitric oxide(NO),ROS,cyclooxygenase-2,inducible NO synthase,IL-6,and TNF-alpha(Pcognitive and locomotor impairments in mice.The fingerprinting analysis showed distinctive peaks with rutin,kaempferol-3-O-glucoside,and anethole as identifiable compounds.Conclusions:Foeniculum vulgare extract can ameliorate LPS-stimulated neuroinflammatory responses in BV-2 microglial cells and improve cognitive and locomotor performance in LPS-administered mice.

关键词： Foeniculum vulgare Microglia Lipopolysaccharide Antioxidant Neuroinflammation MAPK signaling Cognition

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General Optimal Trajectory Planning:Enabling Autonomous Vehicles with the Principle of Least Action

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Engineering 2024年第2期33卷 63-76页

作者： Heye Huang Yicong Liu Jinxin Liu Qisong Yang Jianqiang Wang David Abbink Arkady Zgonnikov School of Vehicle and Mobility Tsinghua UniversityBeijing 100084China department of cognitive Robotics Faculty of MechanicalMaritime and Materials Engineering(3mE)Delft University of TechnologyDelft 2628Netherlands department of Software Technology Faculty of Electrical EngineeringMathematics and Computer ScienceDelft University of TechnologyDelft 2628Netherlands Xi’an Institute of High-Technology Xi’an 710051China

This study presents a general optimal trajectory planning(GOTP)framework for autonomous vehicles(AVs)that can effectively avoid obstacles and guide AVs to complete driving tasks safely and efficiently.Firstly,we employ the fifth-order Bezier curve to generate and smooth the reference path along the road centerline.Cartesian coordinates are then transformed to achieve the curvature continuity of the generated curve.Considering the road constraints and vehicle dynamics,limited polynomial candidate trajectories are generated and smoothed in a curvilinear coordinate system.Furthermore,in selecting the optimal trajectory,we develop a unified and auto-tune objective function based on the principle of least action by employing AVs to simulate drivers’behavior and summarizing their manipulation characteristics of“seeking benefits and avoiding losses.”Finally,by integrating the idea of receding-horizon optimization,the proposed framework is achieved by considering dynamic multi-performance objectives and selecting trajectories that satisfy feasibility,optimality,and adaptability.Extensive simulations and experiments are performed,and the results demonstrate the framework’s feasibility and effectiveness,which avoids both dynamic and static obstacles and applies to various scenarios with multi-source interactive traffic participants.Moreover,we prove that the proposed method can guarantee real-time planning and safety requirements compared to drivers’manipulation.

关键词： Autonomous vehicle Trajectory planning Multi-performance objectives Principle of least action

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