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Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation

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Neuroscience Bulletin 2012年第1期28卷 49-60页

作者： Yu-Xia Chu Yu-qiu Zhang zhi-qi zhao Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical Neurobiology Fudan University Shanghai 200032 China College of Medicine Jiaxmg University Jiaxing Zhejiang 314001 China

Objective The present study aimed to investigate the potential roles of spinal microglia and downstream molecules in the induction of spinal long-term potentiation （LTP） and mechanical allodynia by tetanic stimulation of the sciatic nerve （TSS）. Methods Spinal LTP was induced in adult male Sprague-Dawley rats by tetanic stimulation of the sciatic nerve （0.5 ms, 100 Hz, 40 V, 10 trains of 2-s duration at l 0-s intervals）. Mechanical allodynia was determined using von Frey hairs. Immunohistochemical staining and Western blot were used to detect changes in glial expression of inter- leukin-18 （IL-l 8） and IL-18 receptor （IL-18R）. Results TSS induced LTP of C-fiber-evoked field potentials in the spinal cord. Intrathecal administration of the microglial inhibitor minocycline （200 ~tg/20 gL） 1 h before TSS completely blocked the induction of spinal LTP. Furthermore, after intrathecal injection of minocycline （200 ~tg/20 ~tL） by lumbar puncture 1 h before TSS, administration of minocycline for 7 consecutive days （once per day） partly inhibited bilateral allodynia. Immunohistochemistry showed that minocycline inhibited the sequential activation of microglia and astrocytes, and IL- 18 was predominantly colocalized with the microglial marker Iba-1 in the spinal superficial dorsal horn. Western blot revealed that repeated intrathecal injection of minocyctine significantly inhibited the increased expression of IL-18 and IL- 18Rs in microglia induced by TSS. Conclusion The IL-18 signaling pathway in microglia is involved in TSS-induced spinal LTP and mechanical allodynia.

关键词： long-term potentiation allodynia glia interleukin-18

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Effect of surface acidity and pore size of Al-substituted plugs-containing SBA-15 and MCM-41 silicas on the polymerization of THF

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Chinese Chemical Letters 2011年第1期22卷 105-108页

作者： zhi qi Jia Ming zhao Chun Guang Gao Yong Xiang zhao School of Chemistry and Chemical Engineering Shanxi University Engineering Research Center for Fine Chemicals of Ministry of Education Taiyuan 030006 China

We reported here the simultaneous influence of surface acidity and pore size of M-substituted hexagonal mesoporous silicas （Al- doped plugs-containing SBA-15 and M-doped MCM-41） on polymerization of THE These materials were directly synthesized by introduced aluminum isopropoxide into reaction mixture including surfactant and siliceous precursor. Al-doped plugs-containing SBA-15 （denotes as PAS） samples not only possess typical two-step desorption isotherms, which implied PAS materials generated plugs in their mesochannel, but also exhibit larger pore size and thicker wall than that of Al-doped MCM-41 （denotes as ACM）, which implied PAS would have a great advantage on catalytic reaction involving large molecular （e.g. polymer of THF） in industrial point＇of view. To investigate catalytic activity of PAS and ACM with moderate acidic sites the polymerization of THF in the presence of acetic anhydride was carried out. The results showed PAS exhibiting good performance on polymerization of THF. Such result could be related to the large pore size and moderate acidic sites.

关键词： Hexagonal mesostructure Polymerization THF Acidity Pore size

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Ligustrazine inhibits high voltage-gated Ca^(2+) and TTX-resistant Na^+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

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Neuroscience Bulletin 2006年第2期22卷 79-84页

作者： Bi-Hua BIE Yong CHEN zhi-qi zhao Institute of Shanghai Physiology Chinese Academy of Sciences Shanghai 200031 China Institute of Neurobiology Fu-Dan University Shanghai 200433 China

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinociceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency （PWL） to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion （DRG） neurons. Results Intraplantar injection of ligustrazine （0.5 mg in 25 μl） significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion （DRG） neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin （TTX） -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron .in the rat.

关键词： ligustrazine nociception dorsal root ganglion sodium channel calcium channel

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Activation of glycine site and GluN2B subunit of NMDA receptors is necessary for ERK/CREB signaling cascade in rostral anterior cingulate cortex in rats:Implications for affective pain

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Neuroscience Bulletin 2012年第1期28卷 77-87页

作者： Hong Cao Wen-Hua Ren Mu-Ye Zhu zhi-qi zhao Yu-qiu Zhang Institutes of Neurobiology Institute of Brain Science and State Key Laboratory of Medical Neurobiology Shanghai Medi-cal College Fudan University Shanghai 200032 China Department of Life Science Fudan University Shanghai 200433 China

Objective The rostral anterior cingulate cortex （rACC） is implicated in processing the emotional component of pain. N-methyl-D-aspartate receptors （NMDARs） are highly expressed in the rACC and mediate painrelated affect by activating a signaling pathway that involves cyclic adenosine monophosphate （cAMP）/protein ki- nase A （PKA） and/or extracellular regulated kinase （ERK）/cAMP-response element-binding protein （CREB）. The present study investigated the contributions of the NMDAR glycine site and GluN2B subunit to the activation of ERK and CREB both in vitro and in vivo in rat rACC. Methods Immunohistochemistry and Western blot analy- sis were used to separately assess the expression of phospho-ERK （pERK） and phospho-CREB （pCREB） in vitro and in vivo. Double immunostaining was also used to determine the colocalization of pERK and pCREB. Results Both bath application of NMDA in brain slices in vitro and intraplantar injection of formalin into the rat hindpaw in vivo induced significant up-regulation of pERK and pCREB in the rACC, which was inhibited by the NMDAR antago- nist DL-2-amino-5-phospho-novaleric acid. Selective blockade of the NMDAR GluN2B subunit and the glycine- binding site, or degradation of endogenous D-serine, a co-agonist for the glycine site, significantly decreased the up- regulation of pERK and pCREB expression in the rACC. Further, the activated ERK predominantly colocalized with CREB. Conclusion Either the glycine site or the GluN2B subunit of NMDARs participates in the phosphorylation of ERK and CREB induced by bath application of NMDA in brain slices or hindpaw injection of 5% formalin in rats, and these might be fundamental molecular mechanisms underlying pain affect.

关键词： N-methyl-D-aspartate receptor glycine site GIuN2B D-serine extracellular regulated kinase/cAMP-response element-binding protein signaling pathway rostral anterior cingulate cortex

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The O and H isotope characteristics of water from major rivers in China

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Chinese Journal Of Geochemistry 2015年第1期34卷 28-37页

作者： Si-Liang Li Fu-Jun Yue Cong-qiang Liu Hu Ding zhi-qi zhao Xiaodong Li The State Key Laboratory of Environmental Geochemistry Institute of Geochemistry Chinese Academy of Sciences

Isotopic compositions of the water sources and evapotranspiration in large rivers of China are not well explored. In this investigation, d18 O and dD values of water from major large rivers of China are integrated to understand the spatial and temporal variations in the isotopes of water and d-excess. River water samples were collected from the channels and tributaries of the Changjiang, Yellow, Songhua and Liao Rivers in China. Water from upstream was generally enriched with light isotopes relative to that from downstream areas. Water from the Songhua River and upper reach of the Changjiang River has relatively negative isotopic values impacted by latitude and altitude effects, respectively. The spatial pattern showed that d18O-H2 O values in rivers mainly ranged from-9 to-7 % in most of China based on roughly mapped contours, and rivers enriched in light isotopes were primarily located in the Tibetan Plateau and northeast China The slopes of linear regression from the Yellow and Liao Rivers suggested that the loss of water by direct evaporation shifted the isotopes of water, especially in some small tributaries. Additionally, there was a narrow range of low d18OH2 O values from the main channel of rivers during the lowflow season relative to the high-flow season due to influence of the monsoon climate. No distinct spatial variation of d-excess values was found in the rivers of China. However, water samples in some rivers with low d-excess values had high d18 O values, indicating that evaporation in the tributaries has led to significant water loss, especially in tributaries of the Yellow and Liao Rivers.

关键词：中国东北地区同位素特征河流水源长江上游蒸发损失同位素组成时空变化

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MAIN TRANSMITTERS INVOLVED IN PROCESSING PERIPHERAL AND SPINAL NOCICEPTIVE INFORMATION

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神经解剖学杂志 2001年第B7期17卷 41-44页

作者： zhi-qi zhao, PhD Institute of Neurobiology, Fudan University, Shanghai 200433, P. R.. China

The superficial dorsal horn of the spinal cord, where the primary nociceptive afferent fibers terminate, contains a huge of message molecules and their receptors responsible for spinal nociception. The rapidly increasing evidence has particularly shown that glutamate and substance P are the most important transmitters and/or modulators in processing nociceptive information in the spinal cord. Recently emphasis has also

关键词：损伤感受过程中枢神经外周神经调节谷氨酰胺 P物质神经递质受体亚型

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Effects of dexmedetomidine on excitatory synaptic transmission in rat spinal dorsal horn

Effects of dexmedetomidine on excitatory synaptic transmissi...

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中国神经科学学会第十届全国学术会议

作者： Yan Zhang zhi-qi zhao Yu-qiu Zhang Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University Cell Electrophysiology Laboratory Wannan Medical College

Objective To investigate cellular mechanisms underlying the analgesic effects of dexmedetomidine,a selective α2-adrenergic receptor agonist,at spinal *** The whole-cell patch clamp recording and field potential recording were performed on the superficial dorsal horn（SDH,laminae HI） of spinal cord slices with attached dorsal root from juvenile（2-3 weeks） *** synaptic transmission（eEPSCs） and long-term potentiation（LTP）of C-fiber evoked field potentials（fEPSPs） were recorded from SDH neurons by stimulating dorsal root（DR） and Lissauer’s tract（LT） *** We found that eEPSC were rapidly and dose-dependently reduced by bath application of *** amplitude and frequency of spontaneous EPSC（sEPSC）,exogenous N-methyl-D-aspartate（NMDA）-induced currents and α-amino-3-hydroxy-5-methyl-4-isoxazolepropri-anate（AMPA）-induced currents were all ***,slices pretreated with dexmedetomidine showed failed LTP induction compared with control *** These data suggest that dexmedetomidine possibly inhibits excitatory synaptic transmission in rat spinal dorsal horn through pre-synaptic and post-synaptic mechanisms.

关键词： AMPA receptor NMDA receptor LTP dexmedetomidine spinal cord

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Modulation of morphine antinoceptive tolerance in bone cancer pain rats by P2X7 purinoceptor

Modulation of morphine antinoceptive tolerance in bone cance...

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中国神经科学学会第十届全国学术会议

作者： Hui LI zhi-qi zhao Yu-qiu ZHANG Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University

Bone cancer pain is the most severe chronic pain,and morphine is the most effective ***,long-term morphine therapy produces morphine antinociceptive *** far,studies on morphine tolerance are mostly carried out in normal animals,despite that the clinical morphine antinociceptive tolerance occurs only in patients with chronic ***,chronic pathological pain is quite different from normal physiological pain in *** it is more meaningful to study the mechanisms of morphine tolerance in chronic pain animal *** plays an important role in the development of both chronic pain and morphine *** the firsr time,we investigate the role of P2X7 purinoceptor-mediated the activation of spinal microghal p38/MAPK signaling pathway proinflammatory cytokines（***-lβ and IL-18） and astrocytic products（e.g.D-Serine） release,and hypersensitivity of spinal dorsal horn neurons in morphine tolerance in a rat model of bone cancer *** data showed that the chronic morphine treatment for10 days resulted in a significant loss of analgesic potency in both mechanical and thermal nociceptive tests in rats suffered from bone cancer *** expression levels of P2X7R,Ibal-1,IL-18 and IL-lβ in the spinal dorsal horn were remarkably increased,both in bone cancer rats and chronic morphine treated na（i|¨）ve ***,in chronic morphine treated bone cancer rats,spinal Ibal-1 and IL-18 levels were much lower than bone cancer rats without chronic morphine treatment and naive rats chronic with morphine *** results suggest that in chronic pathological pain status,the mechanism of morphine tolerance is more complicated.

关键词： bone cancer pain morphine tolerance P2X7R

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Matrix metalloprotease-9 mediates bone cancer pain via TRPV1 channels in primary sensory neurons

Matrix metalloprotease-9 mediates bone cancer pain via TRPV1...

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中国神经科学学会第十届全国学术会议

作者： Xiao-Meng Zhang zhi-qi zhao Yu-qiu Zhang Institute of Neurobiology Institutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan University

Bone cancer pain,one of the most severe types of chronic pain,affects most patients with advanced *** of bone cancer pain is a clinical challenge because of its complication and little is known about the *** transient receptor potential vanilloid subfamily member 1（TRPV1）,a molecular integrator of painful stimuli,can be modulated by various signal molecules in ***,matrix metalloprotease-9（MMP-9）has been imphcated in neuropathic pain and inflammatory ***,whether MMP-9 involves in bone cancer pain is still not ***,we report that MMP-9 plays a role in the early-phase of bone cancer pain ***-9 was widely expressed in primary sensory neurons,including TRPV1 positive *** days after tumor injection,immunohistochemistry and western blot showed upregulation of MMP-9 and TRPV1 channels in the ipsilateral dorsal root *** administration of MMP-9 inhibitor I for 7 days,from 1 day before surgery to Post Tumor Day 5（PTD5）,produced antinociceptive effect on spontaneous pain,mechanical allodynia,and thermal hyperalgesia in bone cancer *** cell patch clamp recordings revealed that transient puff of MMP-9 potentiated capsaicin-induced TRPV1 currents in medium- or small-diameter DRG ***,we hypothesize that MMP-9might play a role in bone cancer pain via TRPV1 channels.

关键词： MMP-9 TRPV1 bone cancer pain dorsal root ganglion

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SpinalP2X7R contributes to streptozotocin-induced mechanical allodynia in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2020年第2期21卷 155-165页

作者： Cheng-ming NI He-ping SUN Xiang XU Bing-yu LING Hui JIN Yu-qiu ZHANG zhi-qi zhao Hong CAO Lan XU Department of Endocrinology the Affiliated Wuxi People’s Hospital of Nanjing Medical UniversityWuxi 214023China Department of Translational Neuroscience Jing’an District Centre Hospital of ShanghaiInstitutes of Brain ScienceState Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain ScienceFudan UniversityShanghai 200032China Department of Endocrinology the Affiliated Kunshan First People’s Hospital of Jiangsu UniversityKunshan 215300China Department of Emergency Northern Jiangsu People’s HospitalYangzhou UniversityYangzhou 225001China

Painful diabetic neuropathy(PDN)is a diabetes mellitus ***,the mechanisms underlying PDN are still poorly *** triphosphate(ATP)-gated P2X7 receptor(P2X7R)plays a pivotal role in non-diabetic neuropathic pain,but little is known about its effects on streptozotocin(STZ)-induced peripheral ***,we explored whether spinal cord P2X7R was correlated with the generation of mechanical allodynia(MA)in STZ-induced type 1 diabetic neuropathy in *** was assessed by measuring paw withdrawal thresholds and western *** was applied to analyze the protein expression levels and localization of ***-induced mice expressed increased P2X7R in the dorsal horn of the lumbar spinal cord during *** injected intrathecally with a selective antagonist of P2X7R and P2X7R knockout(KO)mice both presented attenuated progression of ***-immunofluorescent labeling demonstrated that P2X7R-positive cells were mostly co-expressed with Iba1(a microglia marker).Our results suggest that P2X7R plays an important role in the development of MA and could be used as a cellular target for treating PDN.

关键词： P2X7 receptor(P2X7R) Mechanical allodynia Streptozotocin Diabetic mice

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