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Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

Neural Regeneration research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li Beijing Key laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration

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Focusing on the tetra-partite synapse in Parkinson’s disease research using human patient-derived neurons

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Neural Regeneration research 2024年第5期19卷 979-981页

作者： Diogo Cordeiro Tchelet Stern Shani Stern University of Haifa Sagol Department of NeurobiologyHaifaIsrael

Parkinson’s disease(PD)was first described as a neurological disease by *** Parkinson in 1817 as a“shaking palsy”.Since that time,much more is known about the pathophysiology of PD yet the disease is still *** hallmark of the disease is often considered Lewy body neural inclusions in the substantia nigra pars compacta and other brain areas,although not all patients have these *** patients exhibit massive neuronal cell loss in the substantia nigra pars compacta,which is associated with the motor symptoms of tremor,bradykinesia,rigidity,and postural *** is the second most common neurodegenerative disease after Alzheimer’s disease with a prevalence of around 1%of individuals over the age of 60.

关键词： patients Alzheimer Focus

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SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice

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research 2024年第3期2023卷 369-389页

作者： Xiujuan Du Yuhua Yan Juehua Yu Tailin Zhu Chu-Chung Huang Lingli Zhang Xingyue Shan Ren Li Yuan Dai Hui LV Xiao-Yong Zhang Jianfeng Feng Wei-Guang Li Qiang Luo Fei Li Developmental and behavioral Pediatric Department Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children's Environmental HealthXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Developmental and behavioral Pediatric Department Shanghai Xinhua Children's HospitalShanghai 200092China National Clinical research Center for Aging and Medicine at Huashan Hospital Institute of Science and Technology for Brain-lnspired IntelligenceMinistry of Education-Key Laboratory of Computational Neuroscience and Brain-lnspired IntelligenceFudan UniversityShanghai 200433China State Key laboratory of Medical neurobiology and Ministry of Education Frontiers Center for Brain Science Institutes of Brain Science and Human Phenom InstituteFudan UniversityShanghai 200032China Shanghai Key laboratory of Brain Functional Genomics(Ministry of Education) School of Life SciencesEast China Normal UniversityShanghai 200062China Department of Rehabilitation Medicine Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Center for Experimental Studies and research The First Affliated Hospital of Kunming Medical UniversityKunming 650032China Shanghai research Center for Brain Science and Brain-lnspired Intelligence Shanghai201210China Institute of Cognitive Neuroscience School of Psychology and Cognitive ScienceEast China Normal UniversityShanghai 200062China.

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

关键词： metabolism impaired reversed

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Migratory mode transition of astrocyte progenitors in the cerebral cortex: an intrinsic or extrinsic cell process?

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Neural Regeneration research 2024年第3期19卷 471-472页

作者： Michio Miyajima Hidenori Tabata Kazunori Nakajima Department of Anatomy Keio University School of MedicineShinjuku-kuTokyoJapan Department of Molecular neurobiology Institute for Developmental ResearchAichi Developmental Disability CenterKasugaiAichiJapan

The cerebral cortex is comprised of properly localized cell types that exert their specific *** the developing brain,cells migrate from the germinal region to their functional locations(Silva et al.,2019;Cossart and Garel,2022).For example,neocortical excitatory neurons are generated in the cerebral ventricular and subventricular zones,move to the developing cortical plate via radial migration,and reside in a radial array of six neuronal layers(Oishi and Nakajima,2018).On the other hand,cortical interneurons are mainly generated in ganglionic eminences,migrate tangentially across the cerebral cortex,and reach their final destinations in the cortex(Lim et al.,2018).The failure of neuronal migration leads to defects in cortical layer *** the mechanisms of neuronal distribution have been well examined,how astrocytes are diffusely distributed in the cortex is still *** are glial cells in the cerebral cortex with several functions,including metabolic support and synapse formation(Abbott et al.,2006;Bosworth and Allen,2017;Allen and Lyons,2018).For example,astrocytes establish synaptic connectivity in the developing brain while they contact numerous synapses and maintain optimal neuronal activity in the adult *** the developing brain,astrocytes are primarily generated from radial glia after the neurogenic *** a certain type of astrocyte called fibrous astrocytes populates the white matter,protoplasmic astrocytes migrate to the cortical plate during neural network formation.

关键词： cerebral migrate Abbott

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The ubiquitin codes in cellular stress responses

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Protein & Cell 2024年第3期15卷 157-190页

作者： Xiangpeng Sheng Zhixiong Xia Hanting Yang Ronggui Hu Key laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key laboratory of Molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China State Key laboratory of Animal Disease Control Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China Department of Neurology State Key Laboratory of Medical NeurobiologyInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceZhongshan HospitalFudan UniversityShanghai 200032China

Ubiquitination/ubiquitylation,one of the most fundamental post-translational modifications,regulates almost every critical cellular process in *** evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses,from exogenous factors to cellular reactions,causing a dazzling variety of functional *** forms of ubiquitin sig-nals generated by ubiquitylation events in specific milieus,known as ubiquitin codes,constitute an intrinsic part of myriad cellular stress *** ubiquitination events,leading to proteolytic turnover of the substrates or just switch in functionality,initiate,regulate,or supervise multiple cellular stress-associated responses,supporting adaptation,homeostasis recovery,and survival of the stressed *** this review,we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses,while discussing how stresses modulate the ubiquitin *** review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

关键词： ubiquitin E3 ligase environmental stresses intercellular stresses stress response homeostasis

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Pathology of pain and its implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2851-2899页

作者： Bo Cao Qixuan Xu Yajiao Shi Ruiyang Zhao Hanghang Li Jie Zheng Fengyu Liu You Wan Bo Wei Department of General Surgery First Medical CenterChinese PLA General HospitalBeijing 100853China Medical School of Chinese PLA Beijing 100853China Neuroscience research Institute and Department of neurobiology School of Basic Medical SciencesKey Laboratory for NeuroscienceMinistry of Education/National Health CommissionPeking UniversityBeijing 100191China

Pain is estimated to affect more than 20%of the global population,imposing incalculable health and economic *** pain management is crucial for individuals suffering from ***,the current methods for pain assessment and treatment fall short of clinical *** from advances in neuroscience and biotechnology,the neuronal circuits and molecular mechanisms critically involved in pain modulation have been *** research achievements have incited progress in identifying new diagnostic and therapeutic *** this review,we first introduce fundamental knowledge about pain,setting the stage for the subsequent *** review next delves into the molecular mechanisms underlying pain disorders,including gene mutation,epigenetic modification,posttranslational modification,inflammasome,signaling pathways and *** better present a comprehensive view of pain research,two prominent issues,sexual dimorphism and pain comorbidities,are discussed in detail based on current *** status quo of pain evaluation and manipulation is summarized.A series of improved and innovative pain management strategies,such as gene therapy,monoclonal antibody,brain-computer interface and microbial intervention,are making strides towards clinical *** highlight existing limitations and future directions for enhancing the quality of preclinical and clinical *** to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice,thereby improving pain management from bench to bedside.

关键词： pain thereby summarized

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Tetherless Optical Neuromodulation:Wavelength from Orange-red to Mid-infrared

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Neuroscience Bulletin 2024年第8期40卷 1173-1188页

作者： Chao Sun Qi Fan Rougang Xie Ceng Luo Bingliang Hu Quan Wang Key laboratory of Spectral Imaging Technology Xi'an Institute of Optics and Precision Mechanics(XIOPM)Chinese Academy of SciencesXi'an 710119China Key laboratory of Biomedical Spectroscopy of Xi'an Key Laboratory of Spectral Imaging TechnologyXIOPMChinese Academy of SciencesXi'an 710119China Department of neurobiology School of Basic MedicineFourth Military Medical UniversityXi'an 710032China

Optogenetics,a technique that employs light for neuromodulation,has revolutionized the study of neural mechanisms and the treatment of neurological disorders due to its high spatiotemporal resolution and cell-type ***,visible light,particularly blue and green light,commonly used in conventional optogenetics,has limited penetration in biological *** limitation necessitates the implantation of optical fibers for light delivery,especially in deep brain regions,leading to tissue damage and experimental *** overcome these challenges,the use of orange-red and infrared light with greater tissue penetration has emerged as a promising approach for tetherless optical *** this review,we provide an overview of the development and applications of tetherless optical neuromodulation methods with long *** first discuss the exploration of orange-red wavelength-responsive rhodopsins and their performance in tetherless optical ***,we summarize two novel tetherless neuromodulation methods using near-infrared light:upconversion nanoparticle-mediated optogenetics and photothermal *** addition,we discuss recent advances in mid-infrared optical neuromodulation.

关键词： Optical neuromodulation Tetherless Orange-red wavelength responding rhodopsins Upconversion nanoparticle-mediated optogenetics Photothermal neuromodulation

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Context Processing in Contextual and Cued Fear Extinction

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Neuroscience Bulletin 2024年第6期40卷 835-839页

作者： Yimu Zhang Chun Xu Yu Gu State Key laboratory of Medical neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceFudan UniversityShanghai200032China Institute of Neuroscience State Key Laboratory of NeuroscienceCenter for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai200031China

Anxiety disorders such as post-traumatic stress disorder(PTSD)are prevalent mental disorders that disturb millions *** disorders often manifest as excessive fear,anxiety,and distress,significantly impacting daily *** fear extinction paradigms in animals were established decades ago and have been widely used in research,providing a scientific basis for exposure therapies for anxiety disorders in humans.

关键词： distress disorders traumatic

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Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons

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National Science Review 2024年第4期11卷 70-83页

作者： Huiying Zhao Jinrong Liu Yujin Shao Xiang Feng Binhan Zhao Li Sun Yijun Liu Linghui Zeng Xiao-ming Li Hongbin Yang Shumin Duan Yan-qin Yu Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine Nanhu Brain-Computer Interface Institute Liangzhu laboratory MOE Frontier Science Center for Brain Science and Brain-Machine Integration State Key Laboratory of Brain-Machine Intelligence Zhejiang University NHC and CAMS Key laboratory of Medical neurobiology Zhejiang University Key laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province School of Medicine Hangzhou City University

The nucleus of Darkschewitsch(ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons(NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot *** and chemogenetic manipulations revealed that NDGABA neurons mediate freezing ***, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray(l PAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part(Gi V). Together,these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from the l PAG to Gi V, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.

关键词： nucleus of Darkschewitsch GABAergic population defensive behavior freezing neural circuitry

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Anti-epileptic and Neuroprotective Effects of Ultra-low Dose NADPH Oxidase Inhibitor Dextromethorphan on Kainic Acid-induced Chronic Temporal Lobe Epilepsy in Rats

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Neuroscience Bulletin 2024年第5期40卷 577-593页

作者： Jing-Jing Yang Ying-Xin Liu Yan-Fang Wang Bi-Ying Ge Ying Wang Qing-Shan Wang Sheng Li Jian-Jie Zhang Ling-Ling Jin Jau-Shyong Hong Sheng-Ming Yin Jie Zhao College of Basic Medical Sciences Dalian Medical UniversityDalian116044China Department of Neurology The First Affiliated Hospital of Dalian Medical UniversityDalian116011China National and Local Joint Engineering research Center for Drug research and Development of Neurodegenerative Diseases Dalian116044China School of Public Health Dalian Medical UniversityDalian116044China neurobiology laboratory National Institute of Environmental Health SciencesNational Institutes of HealthResearch Triangle ParkDurhamNC27709USA

Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy(TLE).We postulated that kainic acid(KA)-Induced status epilepticus triggers microglia-dependent inflammation,leading to neuronal damage,a lowered seizure threshold,and the emergence of spontaneous recurrent seizures(SRS).Extensive evidence from our laboratory suggests that dextromethorphan(DM),even in ultra-low doses,has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative *** results showed that administration of DM(10 ng/kg per day;subcutaneously via osmotic minipump for 4 weeks)significantly mitigated the residual effects of KA,including the frequency of SRS and seizure *** addition,DM-treated rats showed improved cognitive function and reduced hippocampal neuronal *** found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^(phox) and p47^(phox) proteins in KA-induced chronic TLE ***,even after discontinuation of DM treatment,ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects,which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

关键词： Temporal lobe epilepsy Dextromethorphan NADPH oxidase Ultra-low dose

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