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Upregulation of GLAST by GDNF may ameliorate retinal damages in streptozotocin-induced diabetic rats

Upregulation of GLAST by GDNF may ameliorate retinal damages...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Lu WANG,Jun YU,Qin-Qin DENG,Xiong-Li YANG,Yong-Mei ZHONG~* Institute of Neurobiology,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

Objective Increased levels of glutamate in vitreous and/or retinas of patients and animal models of diabetes are believed to contribute to the pathophysiology of neuronal loss in diabetic retinopathy(DP).This study is to explore possible association of morphological changes with the expression of GLAST,a prominent glutamate- aspartate transporter,and if glial cell line-derived neurotrophic factor(GDNF)administration could ameliorate the changed retinal morphology and cell *** All experiments were conducted in 4-week streptozotocin (STZ)-diabetic rats and age-matched normal SD *** was injected into the vitreous space of one eye chosen at random with a total of three times beginning 2 weeks after STZ *** in GLAST protein expression levels were determined by Western blot *** impairments of retinas were evaluated by in situ end labeling of DNA terminal dUTP nick end labeling(TUNEL)analysis and HE *** Western blot analysis showed that GLAST levels were decreased by 61.66%in STZ-treated rat retinas,compared to control(P<0.05). Morphometric analysis of STZ-treated rat retinas revealed that the inner plexiform layer(IPL)was significantly reduced in thickness(P<0.01)and more TUNEL-positive cells were found(P<0.05)in the outer nuclear layer (ONL).GDNF administration remarkably increased GLAST levels by 124.90%,as compared to the vehicle-treated group(P<0.01).Additionally,the number of TUNEL-positive cells in the ONL became lower(P<0.05)and the IPL was rather well preserved in the GDNF-treated ***,intraocular injection of short interfering RNAs (siRNAs)directed against GLAST antagonized the upregulation of GLAST by ***-administration of GLAST siRNA resulted in a significant increase in number of TUNEL-positive cells in the ONL and thinner *** Intraocular administration of GDNF effectively ameliorates retinal damages in STZ-induced diabetic rats,which could be in part due to GDNF

关键词： GLAST GDNF apoptosis diabetic retinopathy

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Effect of chronic unpredictable stress on conditioning fear behavior and somatosensory evoked potential of rats

Effect of chronic unpredictable stress on conditioning fear ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Hong-Ping HUANG~(1,*),Qing-Chun ZHU~1,Feng WANG~2,Bang-An WANG~1,Huan-Huan ZHANG~1,Meng-Ya WANG~1 1 Department of Humanity and Manage,Cell Electrophysiology Lab 2 Department of The Third Medicine,Wannan Medical College,Wuhu 241002,China

Objective Chronic unpredictable stress was commonly used to evoke depression-like behavior in *** present study was undertaken to investigate the effect of chronic unpredictable stress on conditioning fear behavior and somatosensory evoked potential(SEP) of *** correlation of the conditioning fear behavior and SEP was also *** Twenty-seven male SD rats(weight 190-200 g) were random divided into control group and model *** in model group were subjected to chronic unpredictable *** fear behavior of rats was observed with Freeze monitor system and the latency of somatosensory evoked potential was evaluated with Powerlab *** Compared with control group,rats in model group had decreased freezing behavior responded to the sound stimulation during fear memory stage(56.64%±13.78%,n = 13,vs 69.72%±18.10%,n = 14, P<0.05,mean±SD).The latency of SEP decreased in the rats treated with chronic unpredictable stress(70.54±10.13 ms,n = 14 vs 78.46±7.80 ms,n = 14,P<0.05),which had the significant difference between the two group rats. The correlation coefficient of the conditioning fear behavior and SEP was positive(r = 0.507,P<0.05).Conclusion Chronic unpredictable stress inhibited conditioning fear behavior of rats,decreased latency of SEP,which suggests chronic unpredictable stress stimulations active the neurotransmitter network system involved with both conditioning fear behavior and SEP.

关键词： chronic unpredictable stress conditioning fear behavior somatosensory evoked potential rat

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Neuronal damage and blood-retinal barrier disruption in retinal ischemia/reperfusion injury:protective effects of Lycium barbarum polysaccharides

Neuronal damage and blood-retinal barrier disruption in reti...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Amy Cheuk Yin Lo Suk-Yee Li Chung-Man Yeung Raymond Chuen-Chung Chang Kwok-Fai So David Wong Eye Institute Li Ka Shing Faculty of MedicineThe University of Hong Kong Research Center of Heart BrainHormone and Healthy AgingLi Ka Shing Faculty of MedicineThe University of Hong Kong Department of Anatomy Li Ka Shing Faculty of MedicineThe University of Hong Kong

Objective Neuronal cell death,glial cell activation,retinal swelling and oxidative injury are complications in retinal ischemia/reperfusion(I/R) *** barbarum polysaccharides(LBP),extracts from the wolfberries, are good for "eye health" in Chinese *** aim of our present study is to explore the use of LBP in retinal I/R *** Retinal I/R injury was induced by surgical occlusion of the internal carotid *** to induction of ischemia,mice were fed orally with either vehicle(PBS) or LBP(1 mg/kg) once a day for 1 week. Ischemia was maintained for 2 hours and reperfusion was then allowed for 22 ***-embedded retinal sections were *** cells were counted while apoptosis was assessed using TUNEL *** levels of glial fibrillary acidic protein(GFAP),aquaporin-4(AQP4),poly(ADP-ribose)(PAR) and nitrotyrosine (NT) were investigated by *** integrity of blood-retinal barrier(BRB) was examined by IgG extravasation *** Decreased viable cell count and apoptosis were found in the ganglion cell layer (GCL) and the inner nuclear layer(INL) of the vehicle-treated I/R ***,increased retinal thickness, GFAP activation,AQP4 up-regulation,IgG extravasation and PAR expression level were observed in the vehicletreated I/R *** importantly,many of these changes were diminished or abolished in the LBP-treated I/R *** Pre-treatment with LBP for 1 week effectively protected the retina from neuronal death,apoptosis, glial cell activation,aquaporin water channel up-regulation,disruption of BRB and oxidative *** present study suggests that LBP may have a neuroprotective role in ocular diseases in which I/R is a feature.

关键词： Neuronal damage and blood-retinal barrier disruption in retinal ischemia/reperfusion injury:protective effects of Lycium barbarum polysaccharides

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Rosiglitazone rescue amyloid oligomer-mediated synaptic plasticity and synaptic development impairment in rats

Rosiglitazone rescue amyloid oligomer-mediated synaptic plas...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Gui-Lan LIU,Shu-Jun XU,Ru-Yi LIN,Tian-Xiang DENG,Qiao GUAN,Lv LIN,Qin-Wen WANG~* Medical School,Ningbo University,Ningbo 315211,China

Emerging evidence indicates that rosiglitazone,a potent agonist of peroxisome proliferator-activated receptor gamma（PPARγ）,can prevent or attenuate neurodegeneration in Alzheimer's disease（AD）,but the mechanisms underlying this effect remain to be fully *** this study,behavioral testing,electrophysiology methods and live cell imaging technologies were used to investigate the effect of soluble amyloid-βprotein（AP） oligomers on the synaptic plasticity and synaptic development and to find out wether rosiglitazone can rescue the impairment induced by amyloid-βprotein（Aβ） *** found that administration of Aβ oligomers through unilateral hippocampal injection significantly attenuated the memory and cognition in rats during morris water maze test.20μM and 5μM rosiglitazone improved the memory impairment induced by Aβ oligomers,while 0.5μM rosiglitazone has no *** of in vitro electrophysiology showed that incubation of Aβ oligomers（500 nM） for 40 min prior to high frequency stimulation strongly prevented LTP,the inhibition was completely restored after preincubated the slices with rosiglitazone（5μM） for 1 h or rosiglitazone（2μM） for 5 ***-incubated with rosiglitazone（1μM） for 5 h partially restored inhibition of LTP by Aβ,while pre-incubated with rosiglitazone（1μM） for 1 h can not rescue the inhibition of LTP by Aβ.The beneficial effect of rosiglitazone was not abolished by the PPARγ-specific antagonist,***,we observed the role rosiglitazone and Aβ oligomers on synaptic development in cultured hippocampal neurons at 7 days in vitro（DIV7）.We showed that incubation of Aβ oligomers（500 nM） for 3 h significantly decreased dendritic filopodia *** with rosiglitazone alone（5μM） for 24 h did not alter dendritic filopodia density,while it significantly prevented dendritic filopodia density decrease induced by Aβ *** Aβ oligomers nor rosiglitazone has an effect on dendritic filopodia velocity and length. In con

关键词： Aβ AD synapse plasticity synaptic development PPARy rosiglitazone GW9622

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Neuronal NR2B-containing NMDA receptor mediates astrocytic c-Jun N-terminal kinase activation in a rat model of neuropathic pain

Neuronal NR2B-containing NMDA receptor mediates astrocytic c...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Wei WANG,Sheng-Xi WU,Yun-Qing LI~* Department of Anatomy,Histology and embryology K.K.Leung Brain Research Centre,the Fourth Military Medical University,No.169 West Changle Road,Xi'an 710032,China

Objective The N-methyl-D-aspartate receptor(NMDAR) in the superficial dorsal horn is implicated as a major contributor to excitatory *** studies suggest NMDAR also contributes to neuron-astrocyte *** study was performed to elucidate the molecular mechanisms underlying spinal NMDAR-mediated c-Jun N-terminal kinase(JNK) activation in neuropathic *** Animal pain behaviors were evaluated with von-Frey *** cellular distribution of JNK,NR2B receptor,and interleukin-1βwas detected by immunofluorescent double *** activation after different treatments was checked by Western blot ***-time RT-PCR was performed to detect the changes of cytokines mRNA *** After spinal nerve ligation(SNL), the expression of pJNK and GFAP was significantly higher in the ipsilateral dorsal *** was found to be completely colocalized with *** injection of MK-801,a noncompetitive NMDAR antagonist,or Ro25-6981 and ifenprodil,selective antagonists of NR2B subunit,each significantly reduced JNK ***2B was exclusively expressed on neurons,indicating an intercellular effect of NMDAR antagonists on JNK activation. Intrathecal injection of NMDA(twice a day for 3 d) significantly increased JNK ***, NMDAR-related JNK activation could be blocked by nNOS selective inhibitor 7-nitroindazole sodium salt but not by nNOS sensitive guanylyl cyclase ***,nerve injury-induced interleukin-1beta expression was dependent on astrocytic JNK *** targeting NMDAR-nNOS pathway also influenced interleukinlbeta *** Our results suggest a signal transduction cascade combining neuronal NMDAR-nNOS pathway with astrocytic JNK pathway,by which excitatory neuronal transmission and astrocytic activation-induced neuroinflammation are linked,contributing to nerve injury-induced neuropathic pain.

关键词： NMDA receptor c-jun N-terminal kinase astrocyte,spinal cord pain

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Effects of tetramethylpyrazine on trigeminal neuralgia mediated by P2X3 receptor

Effects of tetramethylpyrazine on trigeminal neuralgia media...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Rao-Ping WU,Han LIU,Shu-Yi QIU,Yun GAO~*,Shang-Dong LIANG Department of Physiology,Basic Medical College of Nanchang University,Nanchang 330006,China

Objective Trigeminal neuralgia（TN）is an uncommon disorder characterized by recurrent attacks of lancinating pain in the trigeminal nerve ***（TMP）is one of the alkaloids contained in Ligustrazine which has been used in traditional Chinese medicine as an analgesic for *** study was designed to explore the effects of TMP on the expression of P2X receptor in trigeminal ganglia（TG）of rats with trigeminal neuralgia（TN）.Methods Sprague-Dawley rats were randomly divided into Sham group,TN group and TMP + TN *** right unilateral TN of rat was produced by placing loose chromic gut ligature around the infraorbital nerve （ION）.The expression changes of P2X receptor in TG were detected by immunohistochemistry,Western blotting and RT-PCR on day 15 after *** Mechanical response threshold was observed before operation and 3, 5,7,9,11,13,15 days after *** TN rats,an allodynia in response to mechanical stimulation of the ligated nerve territory was found on post-operative day 9-15（P<0.05）,and TMP significantly decreased behavioral signs of neuropathic pain from the 8th day after *** with the sham rats,the expression of the TG P2X in the TN group rats was significantly increased（P<0.05）.The expression of TG P2X in the TMP + TN group rats is lower than that in the TN group rats（P<0.05）.Conclusion TMP could reduce the expression of P2X in trigeminal neurons in TN *** may indicate that TMP may inhibit the pain transmission of neuropathic pain through down-regulated P2X receptor in the trigeminal ganglia of TN rats.

关键词： trigeminal neuralgia P2X3 receptor tetramethylpyrazine

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Study of oxymatrine on myocardial ischemic signaling mediated by P2X3 receptors in rat superior cervical ganglia

Study of oxymatrine on myocardial ischemic signaling mediate...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Gui-Lin LI,Shuang-Mei LIU,Shang-Dong LIANG~* Department of Physiology,Medical College of Nanchang University,Nanchang,Jiangxi 330006,China

Objective Blood pressure and sympathetic nerve activity are enhanced by signaling of myocardial ischemic（M1）injury mediated by P2X receptors in rat superior cervical ganglia（SCG）.Oxymatrine is a major alkaloid component obtained from sophora roots and has pharmacological effects,e.g.,antiulcer,anti-inflammatory, antiarrhythmic and antitumor *** present study is aimed to explore the effects of oxymatrine（Oxy）on the transmission of myocardial ischemic signalling mediated by P2X receptors in rat *** Systolic blood pressure and heart rate were measured by the non-invasive blood pressure *** expression levels of P2X mRNA and protein were analyzed by immunohistochemistry,in situ hybridization and western blotting in SCG ***（1）The systolic blood pressure and heart rate increased and the expression of P2X receptors upregulated in SCG neurons after myocardial ischemic injury.（2）Oxymatrine reduced the systolic blood pressure and heart rate in myocardial ischemic *** myocardial ischemic rats treated with oxymatrine,the expression levels of P2X mRNA and protein were lower than those in myocardial ischemic *** The myocardial ischemic injury induced an increase in the expression of P2X receptors in SCG *** expression of P2X receptors in SCG neurons subsequently leaded to the aggravated myocardial injury by enhancing blood pressure and sympathetic nerve *** may decrease the expression of P2X receptor and depress the aggravated myocardial injury.

关键词： superior cervical ganglia P2X3 receptor oxymatrine

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Understanding structure and function of acid-sensing ion channels

Understanding structure and function of acid-sensing ion cha...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Tian-Le XU~(1,2) 1 Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031,China 2 Neuroscience Division,Department of Biochemistry and Molecular Cell Biology,Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine,Shanghai 200025,China

The acid-sensing ion channel（ASIC） has a prominent role in tissue pH-sensing and neuronal signalling. Subunits of ASICs are members of the degenerin/epithelial Na channel protein *** date,seven ASIC subunits have been identified:ASIC1a,ASIC1b,ASIC1b2,ASIC2a,ASIC2b,ASIC3,and *** subunit contains cytosolic N and C termini,two alpha-helical transmembrane domains（M1-M2）,and a disulfide-rich multidomain extracellular *** form a variety of homo- and heterotrimeric ion channels that are activated by extracellular acidosis associated with neurotransmission,injury,inflammation and ischemia,triggering membrane depolarization via Na influx into target *** the operating mechanisms of these ion channels could therefore provide the catalyst for further studying ASIC physiology and pharmacology,as well as promoting the development of experimental techniques for other families of ion channels and/or *** this talk,I will present our current work on ASIC structure and function,in particular those of ASIC1a and ASIC3 *** in this area has been stimulated in recent years by the publication of high-resolution structures of ASIC1,which have permitted the structure-directed approaches and the creation of ASIC homology models.I will first discuss the crucial roles of ASICs in mediating neuronal injury and pain *** a series of computational,chemical and functional approaches,and nonproton ligands（GMQ,agmatine and amiloride） as probes,I will then delineate the nonproton ligand sensing domain in ASIC3 channels at the atomic level and describe how chemical biology,homology modeling and ligand docking can provide useful information about ligand interactions.I will also consider some of the ongoing projects in my laboratory that are investigating the pathophysiological roles of ASICs using ASIC subunit gene knockout *** report ends with a discussion on the generality of ASICs as a model system for the study of struc

关键词： Understanding structure and function of acid-sensing ion channels

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Peripheral inflammation induces promoter demethylation of endogenous hydrogen sulfide synthesis enzyme CBS in rat dorsal root ganglion

Peripheral inflammation induces promoter demethylation of en...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： You-Lang ZHOU~1,Fei-Hu QI~1,Ning-Ang LIU~2,Guang-Yin XU~(1,2,*) 1 Jiangsu Key Laboratory of Neuroregeneration,Nantong University Medical College,Nantong 226001,China 2 Institute ofNeuroscience,Key Laboratory of Pain Research & Therapy,Soochow University,Suzhou 215123,China

Objective Chronic pain associated with inflammation is a common clinical problem,and the underlying mechanisms have only begun to be *** sulfide（HS）,an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However,the molecular and epigenetic mechanisms for expression of HS synthesizing enzyme cystathioninebeta -synthetase（CBS） in peripheral nociceptive processing remain *** present study is to explore the role of CBS gene promoter methylation following peripheral *** Complete Freund's adjuvant（CFA） was injected into plantar surface（100 ml each） of hindpaw of adult male Sprague Dawley rats（6-8 week old）.Realtime polymerase chain reaction（qPCR） and Western blot analysis were employed to measure expression of mRNA and protein in lumbar dorsal root ganglion（DRGs,L4-L6） from control and CFA-treated rats,*** PCR（MSP） and bisulfite sequencing（BSP） were carried out for determining methylation status of the cbs gene *** Peripheral inflammation significantly reduced hind paw withdrawal threshold and remarkably upregulated expression of CBS at both protein and mRNA levels in DRGs when compared with control *** ratio of methylated and unmethylated CpG island for MSP primers（+325～+425;+657～+767） was markedly reduced in inflammatory rats when compared with control *** sequencing of the bisulfite-treated cbs promoter dem- onstrated that the fragment（F210bp,+496 bp～+705 bp） of cbs promoter region,which contains 11 CpG sites was significantly demethylated in DRGs 3 days after CFA ***,expression of MBD4 and Gadd45a was highly enhanced in CFA-treated rats while expression of DNMT3a and 3b was not significantly *** Our data suggest that peripheral inflammation leads to an active DNA demethylation in cbs gene promoter region,thus contributing to the enhanced C

关键词： cystathionine-beta-synthetase dorsal root ganglion inflammatory pain methylation-specific polymerase chain reaction and bisulfite sequencing

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Ginkgolide B attenuates ethanol-induced neurotoxicology through regulating NADPH oxidases

Ginkgolide B attenuates ethanol-induced neurotoxicology thro...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xiu-Juan TIAN,Yi LUO,Xian-Fang MENG~* Department of Neurobiology,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Objective Ethanol has long been demonstrated to trigger cell apoptosis in the central nervous *** over-production of reactive oxygen species（ROS） is considered as one of the most important mechanisms involving in the apoptosis caused by *** B（GB）,which was widely used as a monomer of traditional Chinese medicine,was reported to scavenge free radicals in endothelial cells and smooth muscle ***,whether GB can prevent ethanol-induced neuro-cytotoxicity is still *** aim of this study was to investigate effects of GB on ethanol-induced cytotoxicity,oxidative stress and apoptosis,and to explore potential protective molecular mechanism of *** Effects of GB on ethanol-induced cytotoxicity were detected by MTT and LDH *** death and apoptosis were detected by flow ***-3 activity and ROS were determined by *** peroxidation was also *** of NOX2 and p47 was detected by real-time reverse transcription polymerase chain reaction and Western blot *** oxidase activity was measured by SOD-inhibitable cytochrome c ***（1） When PC12 cells were pretreated with different concentration of GB,cell viability was significantly increased and LDH leakage was decreased in a dose-dependent manner（P<0.05,as compared with control）.（2） A significant increase in caspase-3 activity was found in PC12 cells incubated with ethanol for 24 h,and pretreatment of GB decreased caspase-3 activity（P<0.05）.（3） MDA level in GB-pretreated cells was significantly lower than that treated with ethanol alone（P<0.05）.（4） By RT-PCR and Western blot analysis,we found that ethanol upregulated expression of ROS-generating NOX family members including NOX2 and ***,GB attenuated NADPH activities induced by ethanol.（5） Ethanol-induced production of ROS was significantly decreased in cells treated with *** Ginkgolide B attenuates ethanol-induced neurotoxicology through regulat

关键词： ethanol apoptosis reactive oxygen species NADPH oxidases

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