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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS Key Laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of Sciences BeijingChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter

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Stability of rat models of fluid percussion-induced traumatic brain injury: comparison of three different impact forces

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Neural regeneration Research 2015年第7期10卷 1088-1094页

作者： Yun-peng Lin Rong-cai Jiang Jian-ning Zhang Department of Neurosurgery Tianjin Medical University General Hospital Tianjin Neurological institute Key Laboratory of Post-trauma Neurorepair and regeneration in Central Nervous System Ministry of Education Tianjin Key Laboratory of Injuries Variations and Regeneration of Nervous System Tianjin Medical University General Hospital

Fluid percussion-induced traumatic brain injury models have been widely used in experimental research for years. In an experiment, the stability of impaction is inevitably affected by factors such as the appearance of liquid spikes. Management of impact pressure is a crucial factor that determines the stability of these models, and direction of impact control is another basic element. To improve experimental stability, we calculated a pressure curve by generating repeated impacts using a fluid percussion device at different pendulum angles. A stereotactic frame was used to control the direction of impact. We produced stable and reproducible models, including mild, moderate, and severe traumatic brain injury, using the MODEL01-B device at pendulum angles of 6°, 11° and 13°, with corresponding impact force values of 1.0 ± 0.11 atm（101.32 ± 11.16 k Pa）, 2.6 ± 0.16 atm（263.44 ± 16.21 k Pa）, and 3.6 ± 0.16 atm（364.77 ± 16.21 k Pa）, respectively. Behavioral tests, hematoxylin-eosin staining, and magnetic resonance imaging revealed that models for different degrees of injury were consistent with the clinical properties of mild, moderate, and severe craniocerebral injuries. Using this method, we established fluid percussion models for different degrees of injury and stabilized pathological features based on precise power and direction control.

关键词： nerve regeneration traumatic brain injury fluid percussion impact force pressure curve head fixed impact peak animal models neural regeneration

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Neutrophil extracellular traps mediate neuro-immunothrombosis

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Neural regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo Lou Jianning Zhang Quanjun Deng Xin Chen Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry *** extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation ***,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and *** summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic *** blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological *** research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of ***,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain *** review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

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Aberrant nuclear lamina contributes to the malignancy of human gliomas

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Journal of Genetics and Genomics 2022年第2期49卷 132-144页

作者： Shunqi Pei Xuehui Wang Xuan Wang Hao Huang Huaping Tao Binghua Xie Aifen Yang Mengsheng Qiu Zhou Tan institute of Life Sciences Key Laboratory of Organ Development and Regeneration of Zhejiang ProvinceCollege of Life SciencesHangzhou Normal UniversityZhejiang 311121China

Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.

关键词： Gliomas Proteomics Genomics Nucleus Lamins Malignancy

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Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era

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National Science Review 2022年第10期9卷 230-242页

作者： Chun Xu Chang Lei Sepanta Hosseinpour Saso Ivanovski Laurence J.Walsh Ali Khademhosseini School of Dentistry The University of Queensland Centre for Orofacial regeneration Reconstruction and Rehabilitation (COR3) School of Dentistry The University of Queensland Australian institute for Bioengineering and Nanotechnology The University of Queensland Terasaki institute for Biomedical Innovation

Following the global COVID-19 pandemic,nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools,vaccines and antiviral treatment for this novel virus(SARS-CoV-2).In this review,we first summarize nanotechnology with regard to the detection of SARS-C oV-2,including nanoparticle-based techniques such as rapid antigen testing,and nanopore-based se quencing and sensing *** we investigate nanote chnology as it applies to the development of COVID-19 vaccines and anti-SARS-CoV-2 *** also highlight nanotechnology for the post-pandemic era,by providing tools for the battle with SARS-C oV-2 variants and for enhancing the global distribution of *** not only contributes to the management of the ongoing COVID-19 pandemic but also provides platforms for the prevention,rapid diagnosis,vaccines and antiviral drugs of possible future virus outbreaks.

关键词： COVID-19 nanotechnology SARS-CoV-2 diagnosis vaccines

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Hydroxysafflor yellow A improves learning and memory in a rat model of vascular dementia by increasing VEGF and NR1 in the hippocampus

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Neuroscience Bulletin 2014年第3期30卷 417-424页

作者： Nan Zhang Mengya Xing Yiyi Wang Hao Liang Zhuo Yang Fudong Shi Yan Cheng Department of Neurology Tianjin Medical University General Hospital Tianjin Neurological institute Key Laboratory of Post-traumatic Neuro-repair and regeneration in the Central Nervous System Ministry of Education Tianjin Key Laboratory of Injuries Variations and Regeneration of the Nervous System Tianjin Haihe Hospital Nankai University

Hydroxysafflor yellow A （HSYA） has angiogenesis- regulating and neuro-protective effects, but its effects on vascular dementia （VaD） are unknown. In this study, 30 adult Sprague-Dawley rats were. randomly allocated to five groups： normal, sham-operation, VaD alone （bilateral carotid artery occlusion）, VaD plus saline （control）, and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all five groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation （LTP） method. Vascular endothelial growth factor （VEGF） and N-methyi-D- aspartic acid receptor 1 （NR1） expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze （P 〈0.05）, and the LTP at CA3- CA1 synapses in the hippocampus was enhanced （P 〈0.05）. Western blot in the late-phase VaD group showed slight up-regulation of VEGF and down- regulation of NR1 in the hippocampus, while HSYA significantly up-regulated both VEGF and NRI. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.

关键词： vascular dementia hydroxysafflor yellow A long-term potentiation NMDA receptor vascular endothelial growth factor

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Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

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Cellular & Molecular Immunology 2021年第6期18卷 1489-1502页

作者： Lu Shi Hongling Tian Peng Wang Ling Li Zhaoqi Zhang Jiayu Zhang Yong Zhao State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina institute for Stem Cell and regeneration Chinese Academy of SciencesBeijingChina

Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

关键词： Microgravity Hematopoietic progenitor cells Macrophage differentiation Macrophage polarization RAS/ERK/NFκB pathway

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Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice

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Neural regeneration Research 2021年第12期16卷 2542-2548页

作者： Zhong-Hai Huang Ai-Ying Feng Jing Liu Libing Zhou Bing Zhou Panpan Yu Guangdong-Hong Kong-Macao institute of Central Nervous System regeneration Ministry of Education Joint International Research Laboratory of Central Nervous System RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Interdisciplinary Innovation institute of Medicine and Engineering Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang UniversityBeijingChina

Inhibitor of DNA binding 2(Id2)can promote axonal regeneration after injury of the central nervous ***,whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently *** this study,we established a mouse model of bilateral sciatic nerve crush *** weeks before injury,AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal *** results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve,and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury,arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius *** 1 month after injury,extensive neuromuscular reinnervation *** addition,the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered,and their latency was *** findings suggest that Id2 can accelerate axonal regeneration,promote neuromuscular reinnervation,and enhance functional improvement following sciatic nerve ***,elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following *** study was approved by the Experimental Animal Ethics Committee of Jinan University(approval No.20160302003)on March 2,2016.

关键词： axonal regeneration functional recovery inhibitor of DNA binding 2 motor neuron neuromuscular junctions peripheral nerve reinnervation sciatic nerve injury

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Genetically modified non-human primate models for research on neurodegenerative diseases

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Zoological Research 2024年第2期45卷 263-274页

作者： Ming-Tian Pan Han Zhang Xiao-Jiang Li Xiang-Yu Guo Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hongkong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China

Neurodegenerative diseases(NDs)are a group of debilitating neurological disorders that primarily affect elderly populations and include Alzheimer's disease(AD),Parkinson's disease(PD),Huntington's disease(HD),and amyotrophic lateral sclerosis(ALS).Currently,there are no therapies available that can delay,stop,or reverse the pathological progression of NDs in clinical *** the population ages,NDs are imposing a huge burden on public health systems and affected *** models are important tools for preclinical investigations to understand disease pathogenesis and test potential *** numerous rodent models of NDs have been developed to enhance our understanding of disease mechanisms,the limited success of translating findings from animal models to clinical practice suggests that there is still a need to bridge this translation *** World nonhuman primates(NHPs),such as rhesus,cynomolgus,and vervet monkeys,are phylogenetically,physiologically,biochemically,and behaviorally most relevant to *** is particularly evident in the similarity of the structure and function of their central nervous systems,rendering such species uniquely valuable for neuroscience ***,the development of several genetically modified NHP models of NDs has successfully recapitulated key pathologies and revealed novel *** review focuses on the efficacy of NHPs in modeling NDs and the novel pathological insights gained,as well as the challenges associated with the generation of such models and the complexities involved in their subsequent analysis.

关键词： Neurodegeneration Non-human primate Macaque monkey Animal model Gene modification

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Pharmacological intervention for chronic phase of spinal cord injury

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Neural regeneration Research 2025年第5期20卷 1377-1389页

作者： Chihiro Tohda Section of Neuromedical Science Institute of Natural MedicineUniversity of ToyamaToyamaJapan

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidat

关键词： axonal growth chronic phase clinical study pharmacotherapy spinal cord injury

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