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Spinal CCL2 Promotes Central Sensitization, Long-Term Potentiation, and Inflammatory Pain via CCR2： Further Insights into Molecular, Synaptic, and Cellular Mechanisms

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Neuroscience Bulletin 2018年第1期34卷 13-21页

作者： Rou-Gang xie Yong-Jing Gao Chul-Kyu Park Ning Lu Ceng Luo Wen-Ting Wang sheng-xi wu Ru-Rong Ji Department of Neurobiology and Collaborative Innovation Center for Brain Science The Fourth Military Medical University Xi'an 710032 China Department of Anesthesiology Duke University Medical Center Durham NC 27710 USA Pain Research Laboratory Institute of Nautical Medicine Jiangsu Key laboratory of Neuroregeneration Nantong University Nantong 226001 China Department of Physiology College of Medicine Gachon University Incheon 21999 Republic of Korea Institutes of Brain Science and State Key Laboratory of Medical Neurobiology Collaborative Innovation Center for Brain Science Fudan University Shanghai 200032 China Department of Neurobiology Duke University Medical Center Durham NC 27710 USA

Mounting evidence supports an important role of chemokines, produced by spinal cord astrocytes, in promoting central sensitization and chronic pain. In particular, CCL2 （C-C motif chemokine ligand 2） has been shown to enhance N-methyl-D-aspartate （NMDA）-induced currents in spinal outer lamina II （Iio） neurons. However, the exact molecular, synaptic, and cellular mechanisms by which CCL2 modulates central sensitization are still unclear. We found that spinal injection of the CCR2 antagonist RS504393 attenuated CCL2- and inflammation-induced hyperalgesia. Single-cell RT-PCR revealed CCR2 expres- sion in excitatory vesicular glutamate transporter subtype 2-positive （VGLUT2＋） neurons. CCL2 increased NMDA- induced currents in CCR2＋/VGLUT2＋ neurons in lamina IIo; it also enhanced the synaptic NMDA currents evoked by dorsal root stimulation; and furthermore, it increased the total and synaptic NMDA currents in somatostatin- expressing excitatory neurons. Finally, intrathecal RS504393 reversed the long-term potentiation evoked in the spinal cord by C-fiber stimulation. Our findings suggest that CCL2 directly modulates synaptic plasticity in CCR2- expressing excitatory neurons in spinal lamina Iio, and this underlies the generation of central sensitization in patho- logical pain.

关键词： Chemokines C-C motif chemokine ligand 2 (CCL2) Monocyte chemoattractant protein 1 (MCP-1) Neuron-glial interaction

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Activation of Cannabinoid Receptor 1 in GABAergic Neurons in the Rostral Anterior Insular Cortex Contributes to the Analgesia Following Common Peroneal Nerve Ligation

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Neuroscience Bulletin 2023年第9期39卷 1348-1362页

作者： Ming Zhang Cong Li Qian Xue Chang-Bo Lu Huan Zhao Fan-Cheng Meng Ying Zhang sheng-xi wu Yan Zhang Hui Xu Department of Neurobiology and Collaborative Innovation Center for Brain Science School of Basic MedicineThe Fourth Military Medical UniversityXi’an710032China Department of Anesthesiology Heze Municipal HospitalHeze274031China Department of Cardiovascular Surgery Xi’an International Medical Center HospitalXi’an710100China Department of Basic Medical Laboratory The General Hospital of Western Theater CommandChengdu610083China

The rostral agranular insular cortex(RAIC)has been associated with pain *** the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive under the neuropathic pain *** pain was induced in C57BL/6 mice by common peroneal nerve(CPN)*** roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice,glutamatergic,or GABAergic neuron cannabinoid receptor 1(CB1R)knockdown mice with the whole-cell patch-clamp and pain behavioral *** E/I ratio(amplitude ratio between mEPSCs and mIPSCs)was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated ***-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated *** analgesic effect of ACEA(a CB1R agonist)was alleviated along with bilateral dorsolateral funiculus lesions,with the administration of AM251(a CB1R antagonist),and in CB1R knockdown mice in GABAergic neurons,but not glutamatergic neurons of the *** results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.

关键词： Rostral agranular insular cortex:Cannabinoid receptor 1-Neuropathic pain Dorsolateral fasciculus:GABAergic neuron

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Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission

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Neuroscience Bulletin 2021年第4期37卷 478-496页

作者： Wen-Juan Han Sui-Bin Ma Wen-Bin wu Fu-Dong Wang xiu-Li Cao Dong-Hao Wang Hai-Ning wu Rou-Gang xie Zhen-Zhen Li Fei Wang sheng-xi wu Min-Hua Zheng Ceng Luo Hua Han Department of Biochemistry and Molecular Biology School of Basic MedicineFourth Military Medical UniversityXi’an710032China Department of Neurobiology School of Basic MedicineFourth Military Medical UniversityXi’an710032China The Fourth Regiment School of Basic MedicineFourth Military Medical UniversityXi’an710032China Department of Medical Genetics and Developmental Biology Fourth Military Medical UniversityXi’an710032China National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China Key Laboratory of Medicinal Resources and Natural Pharmaceutical ChemistryMinistry of EducationCollege of Life SciencesShaanxi Normal UniversityXi’an710119China

Tweety-homolog 1(Ttyh1)is expressed in neural tissue and has been implicated in the generation of several brain ***,its functional significance in pain processing is not *** disrupting the gene encoding Ttyh1,we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice,along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey(PAG)in the basal *** importantly,the peripheral inflammationevoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient *** of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter *** with Ttyh1 specifically in nociceptors produces a comparable pain ***,in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

关键词： Ttyh1 Inflammatory pain Peripheral sensitization Long-term potentiation

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Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina Ⅱ Neurons

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Neuroscience Bulletin 2020年第11期36卷 1344-1354页

作者： Hui Zhang Sui-Bin Ma Yong-Jing Gao Jun-Ling xing Hang xian Zhen-Zhen Li Shu-Ning Shen sheng-xi wu Ceng Luo Rou-Gang xie Department of Neurobiology Fourth Military Medical UniversityXi'an 710032China Department of Health Statistics Fourth Military Medical UniversityXi'an 710032China Pain Research Laboratory Institute of Nautical MedicineJiangsu Key laboratory of NeuroregenerationNantong UniversityNantong 226001China Department of Radiation Biology Faculty of Preventive MedicineFourth Military Medical UniversityXi'an 710032China Department of Orthopedics Xijing HospitalFourth Military Medical UniversityXi'an 710032China Department of Stomatology No.984 Hospital of the People's Liberation ArmyBeijing 100094China

Previous studies have shown that CCL2(C-C motif chemokine ligand 2)induces chronic pain,but the exact mechanisms are still ***,we established models to explore the potential *** experiments revealed that an antagonist of extracellular signal-regulated kinase(ERK)inhibited not only CCL2-induced inflammatory pain,but also pain responses induced by complete Freund’s *** posed the question of the intracellular signaling cascade *** experiments showed that CCL2 up-regulated the expression of phosphorylated ERK(pERK)and N-methyl D-aspartate receptor[NMDAR]subtype 2B(GluN2B);meanwhile,antagonists of CCR2 and ERK effectively reversed these ***-cell patchclamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway,which was blocked by antagonists of GluN2B and *** summary,we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents,eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway.

关键词： C-C motif chemokine ligand 2 Monocyte chemoattractant protein 1 Neuron-glial interaction Extracellular signal-regulated kinase

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Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery

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Neural Regeneration Research 2022年第8期17卷 1814-1820页

作者： Kun Zhang Wen-Can Lu Ming Zhang Qian Zhang Pan-Pan xian Fang-Fang Liu Zhi-Yang Chen Chung Sookja Kim sheng-xi wu Hui-Ren Tao Ya-Zhou Wang Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration Tongji UniversityShanghaiChina Department of Spine Surgery Shenzhen University General HospitalShenzhenGuangdong ProvinceChina Department of Neurology Hainan Hospital of Chinese PLA General HospitalSanyaHainan ProvinceChina Department of Anesthesiology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Faculty of Medicine Macao University of Science and TechnologyMacao Special Administrative RegionChina

Neural stem cell(NSC)transplantation is a promising strategy for replacing lost neurons following spinal cord ***,the survival and differentiation of transplanted NSCs is limited,possibly owing to the neurotoxic inflammatory *** of the important role of glucose metabolism in M1/M2 polarization of microglia/macrophages,we hypothesized that altering the phenotype of microglia/macrophages by regulating the activity of aldose reductase(AR),a key enzyme in the polyol pathway of glucose metabolism,would provide a more beneficial microenvironment for NSC survival and ***,we reveal that inhibition of host AR promoted the polarization of microglia/macrophages toward the M2 phenotype in lesioned spinal cord injuries.M2 macrophages promoted the differentiation of NSCs into neurons in *** of NSCs into injured spinal cords either deficient in AR or treated with the AR inhibitor sorbinil promoted the survival and neuronal differentiation of NSCs at the injured spinal cord site and contributed to locomotor functional *** findings suggest that inhibition of host AR activity is beneficial in enhancing the survival and neuronal differentiation of transplanted NSCs and shows potential as a treatment of spinal cord injury.

关键词： aldose reductase functional recovery inflammation macrophage microglia neural stem cell transplantation neuronal differentiation polarization spinal cord injury

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Characteristics of traumatic brain injury models:from macroscopic blood flow changes to microscopic mitochondrial changes

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Neural Regeneration Research 2023年第10期18卷 2268-2277页

作者： Ding-Ding Yang xiang-Dong Wan An-Di Chen Zi-Qian Yan Yi-Fan Lu Jun-Chen Liu Ya-Zhou Wang Jing Wang Yan Zhao sheng-xi wu Guo-Hong Cai Department of Neurobiology School of Basic MedicineForth Military Medical UniversityXi’anShaanxi ProvinceChina Hebei Medical University ShijiazhuangHebei ProvinceChina College of Life Sciences&Research Center for Resource Peptide Drugs Yan’an UniversityYan’anShaanxi ProvinceChina Department of Nuclear Medicine First Affiliated Hospital of Forth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Gastroenterology First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model.A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of>2 mm is used to induce severe brain ***,the different effects and underlying mechanisms of these two model types have not been *** study investigated the changes in cerebral blood flow,differences in the degree of cortical damage,and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3,4,and 5 m/*** also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute(7 days)and chronic phases(30 days).The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased,and swelling and bulging of brain tissue,increased vascular permeability,and large-scale exudation *** the 2 mm group,the main pathological changes were decreased cerebral blood flow,brain tissue loss,and cerebral vasospasm occlusion in the injured *** motor and cognitive impairments were found on day 7 after injury in the 2 mm group;at 30 days after injury,the motor function of the 2 mm group mice recovered significantly while cognitive impairment *** sequencing showed that compared with the 1 mm group,the 2 mm group expressed more ferroptosis-related *** changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7,the mitochondria in both groups shrank and the vacuoles became larger;on day 30,the mitochondria in the 1 mm group became larger,and the vacuoles in the 2 mm group remained *** analyzing the proportion of mitochondrial subgroups in different groups,we found that the model mice had different patterns of mitochondrial composition at different time periods,suggesting that the differenc

关键词： cerebral blood flow cognitive impairments controlled cortical impingement ferroptosis mitochondrial dysfunction motor impairments mouse model traumatic brain injury

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Dissolution behaviors of rare earth elements in phosphoric acid solutions

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Transactions of Nonferrous Metals Society of China 2018年第11期28卷 2376-2383页

作者： sheng-xi wu Long-sheng ZHAO Liang-shi WANG xiao-wei HUANG Jin-shi DONG Zong-yu FENG Da-li CUI Li-feng ZHANG National Engineering Research Center for Rare Earth Materials GRINM Group Co.Ltd.Beijing 100088China School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing 100083China

In order to provide practical fundamental data for rare-earth elements （REEs） recovery from phosphoric acid and to betterunderstand REEs behavior during the phosphoric acid evaporation process, the solubilities of REEs in phosphoric acid with variousconcentrations of phosphorus at different temperatures were measured. A simple linear model between REEs solubility andphosphoric acid concentration is built and the experimental data are found to fit it very well （R2〉0.94）. Hydrogen-ion concentration isfound to be the predominant factor controlling the solubility of REEs in phosphoric acid. In addition, the solubility of REEs inphosphoric acid is found to sharply decrease with increasing temperature, which can be attributed to the increase of the Gibbs energyof the REEPO4 dissolution reaction or the restraint of the disassociation of phosphoric acid molecules owing to the elevatedtemperature.

关键词： rare earth elements phosphoric acid dissolution behavior rare earth phosphates temperature

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The role of Brd2 in the development of cerebral cortex

The role of Brd2 in the development of cerebral cortex

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中国神经科学学会第十二届全国学术会议

作者： Jing HUANG Cong-Qing ZHAN Jing Chen Yun-Qing Li sheng-xi wu Department of Anatomy Histology and Embryology K.K.Leung Brain Research Centre The Fourth Military Medical University Department of Neurobiology and Collaborative Innovation Center for Brain Science Fourth Military Medical University

Objective Bromodomain-containing protein 2（Brd2） is one of four BET（bromodomain and extra-terminal domain） family members. Various functions have been ascribed to the Brd2, including cellular proliferation, apoptosis and transcription. However, little is known about the potential function of Brd2 in the development of cerebral cortex. Methods To understand further the precise function of Brd2 in cortical development, fluorescent in situ hybridization combined with immunofluorescent histochemistry were used to detect the expression and feature of Brd2 in the cerebral cortex. We used the technique of in utero electroporation and silenced Brd2 successfully in subsets of neural progenitors in the developing mouse cortex. Results Brd2 is most abundant in the cerebral cortex. Brd2 is highly expressed in neurons but is undetectable in glial cells, indicating an important role of Brd2 in neuronal function. Down regulating Brd2 by RNA interference in cerebral cortex induced cortical development abnormalities. Conclusion Our findings reveal an important role of Brd2 in the development of cerebral cortex.

关键词： Brd2 cerebral cortex development in utero electroporation

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Mathematical model and reaction mechanism of molybdenum and tungsten extraction with TRPO from peroxide solution

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Transactions of Nonferrous Metals Society of China 2022年第9期32卷 3123-3135页

作者： xin-bing xiA Gui-qing ZHANG Wen-juan GUAN Li ZENG sheng-xi wu Qing-gang LI Zuo-ying CAO School of Metallurgy and Environment Central South UniversityChangsha 410083China Key Laboratory of Metallurgical Separation Science and Engineering in Nonferrous Industry Central South UniversityChangsha 410083China Key Laboratory of Hunan Province for Metallurgy and Material Processing of Rare Metals Changsha 410083China

To understand the behavior of molybdenum and tungsten extracted by tri-alkyl phosphine oxide(TRPO)from peroxide solution,the extraction mechanism was studied by slope method and Raman and FTIR *** empirical formulas of molybdenum and tungsten extraction distribution ratio(D_(Mo)and D_(W))as functions of equilibrium pH,TRPO concentration and temperature were obtained by establishing mathematical ***,the reliability of the empirical formula was verified in the H^(+)-W-Mo-H_(2)O_(2) *** results indicate that the calculated values of D_(Mo)or D_(W)were consistent with the experimental *** apparent extraction equilibrium constants of molybdenum and tungsten wereK_(Mo)^(app)=8.51×10^(3)(0.74≤pH_(e)≤1.7),K_(Mo)^(app)=99.89×10^(3)(1.7

关键词： tungsten molybdenum solvent extraction tri-alkyl phosphine oxide(TRPO) hydrogen peroxide(H_(2)O_(2))

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Intermittent hypoxia induced dynamic changes in dendritic mitochondrial ultrastructure and cytochrome oxidase activity in the pre-B?tzinger complex of rats

Intermittent hypoxia induced dynamic changes in dendritic mi...

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第七届全国呼吸系统重大疾病转化医学学术论坛

作者： Ying-Ying Liu Jun-Jun Kang Baolin Guo sheng-xi wu xiao-Feng Huang Department of Neurobiology The Fourth Military Medical University

＜正＞AIM:Mitochondria,as primary energy generators and Ca2+biosensor,are dynamically coupled to neuronal activities,and thus play a role in *** are located mainly in subcellular regions,especially at synapses where e...

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