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The characteristics of the transmission of enhanced susceptibility after acquired febrile seizure in rats

The characteristics of the transmission of enhanced suscepti...

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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： Bo FENG,Yun-Jian DAI,Deng-Chang WU,Shi-Hong ZHANG,Zhong CHEN~* Department of Pharmacology Key Laboratory of Medical Neurobiology of Ministry of Health of China Zhejiang Province Key Laboratory of Neurobiology College of Pharmaceutical Sciences,Zhejiang University, Hangzhou 310058,China

Objective Early exposure to enriched environment may deeply influence the developing synaptic plasticity and this effect can transmit to *** febrile seizures(FSs) are associated with a risk of subsequent temporal lobe *** this study,we tested whether this acquired enhancement of susceptibility can be transmitted to offspring,and what is the risk factor during this *** Prolonged seizures were evoked by exposing rat pup(9) to a hyperthermic environment of(44±2)℃.Kainic acid,pentylenetetrazol(PTZ) and maximal electroshock(MES) were used to test the seizure susceptibility in rats that experienced FSs(FO) and the susceptibility of seizures in the following 2 generations(Fl,F2) was tested as *** mothers were mated with non-FSs fathers and vice versa to reveal which parent contributed to the transmissional ***(ⅰ) Both MES and kainic acid induced higher scores of seizures in the Fl-FSs rats,while there is no significant difference in PTZ induced seizures compared with those of control rats,(ⅱ) There was no significant difference in scores of MES-induced epilepsy between the F2 control and FSs groups,(ⅲ) Offspring of FO rats that had experienced 10 FSs displayed higher scores to MES-induced seizures than that of offspring in control group and 4*2 FSs group;however, offspring of FO rats that had experienced 4*2 FSs did not display significant difference to MES-induced seizures, (iv) Scores of MES-induced seizures in Fl rats mated by FSs mother and non-FSs father are higher than that by FSs father and non-FSs *** These results indicate that(1) the transgenerational transmission showed severity-dependent and model-dependent characteristics;and(2) the transgenerational transmission was limited to Fl generation through the *** finding may suggest non-Mendelian transgenerational inheritance play a role in the epileptogenesis.

关键词： febrile seizures kainic acid pentylenetetrazol maximal electroshock transmission

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Acute modulation of ASIC3 channels by serotonin contributes to peripheral hyperalgesia

Acute modulation of ASIC3 channels by serotonin contributes ...

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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： Xiang WANG,Tian-Le XU~* Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031,China

Acid-sensing ion channels(ASICs) are proton-gated cation channels and are emerging as key sensors for extracellular protons in central and peripheral *** currents mediated by ASICs inactivate rapidly even in the continuous presence of agonist(protons).Remarkably,type 3 ASIC(ASIC3),which is predominantly distributed in sensory neurons,responds to mild acidosis(pH 6.8-7.2) with a sustained *** characteristics has been proposed to mediate persistent acidic pain associated with arthritis,muscular ischemia,and *** the present study,we investigated acute modulation of ASIC3-containing channels by various inflammatory mediators in both dorsal root ganglia(DRG) neurons and CHO cells expressing ASIC *** found that serotonin(5-HT),a classical proinflammatory mediator,specifically enhanced the sustained currents of homomeric ASIC3 and heteromeric ASIC3/1b ***,5-HT directly acts on ASIC3 channels rather than through 5-HT receptors, because specific receptor antagonists did not affect 5-HT *** importantly,mutations at ASIC3(E79A, E79S,E423A and Q269A) completely abolished 5-HT-induced ***,co-application of 5-HT and acetic acid significantly increased pain-related behaviors as assayed in the paw-licking test in mice,which was largely attenuated in ASIC3-deletion mice and inhibited by the nonselective ASICs inhibitor amiloride but not by 5-HT receptor antagonists methysergide and *** together,these data identify ASIC3 channels as a molecular target for rapid actions of 5-HT and reinforce the importance of ASIC3 channels in regulating inflammatory pain.

关键词： acid-sensing ion channel 3 5-HT hyperalgesia

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Effects of modulation of central nitric oxide signaling on exercise performance in exhausted rats

Effects of modulation of central nitric oxide signaling on e...

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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-Yu LIU~*,Jin-Jua XUE,Jian-Mei CUI,Zhi LI Institute of Sport and Exercise Medicine,North University of China,Taiyuan 030051,China

Objective At present,there have been few reports about whether nitric oxide(NO) in central nervous system is involved in the regulation of exercise performance and fatigue-induced ***,because there is difference among exercise patterns,sampling regions and sampling time,assay methods in published reports,the results about central NO in exercise-induce fatigue were *** picture the relationship between central NO and exercise-induced fatigue,studies were performed to assess(1) the effects of exhaustive exercise on central NO level,(2) the effects of modulation of central NO pathway on rat's exercise performance and NO's role in modulation of fatigue stress through intracerebroventricular(i.c.v.) microinjection of L-arginine(L-Arg),a NO precursor,and L-nitro-arginine methyl ester(I-NAME),a nitric oxide synthase(NOS)*** Rats were randomly assigned to five groups:control group,exhausted group,saline/exhausted group,L-Arg/exhausted group,and I-NAME/ exhausted *** recovery from surgery that a cannula was implanted into the lateral cerebral ventricle of the male SD rats,rats were injected with normal saline,L-Arg or I-NAME for four consecutive ***,a one-time exhaustive treadmill exercise(on the speed of 18 m/min,an inclination of 5°) was *** time of exercise till exhaustion was recorded and total workload was calculated,which represented the running *** levels of nitrate/nitrite(NOx) in plasma,hypothalamus and hippocampus after exhaustive treadmill exercise were assayed by a colorimetric ***(1) Compared with those in the control group,plasma NOx level and usea nitrogen concentration was significantly increased in the exhausted group(P<0.01).The hypothalamic NOx level decreased significantly in the exhausted group(P<0.001),but there was no significant change of NOx level in *** from an open-field test showed that the locomotor activity at pre-surgery,pre-injection and p

关键词： nitric oxide exercise performance L-arginine L-nitro-arginine methyl ester

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Cytokines induce the expression and activity of cathepsin C in microglia in LPS-induced neuroinflammation

Cytokines induce the expression and activity of cathepsin 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： Kai FAN~1,Bin FAN~2,Jian-Mei MA~(1,*) 1 Anatomy department of Dalian Medical University,Dalian 116044,China 2 Graduate school of Dalian Medical University,Dalian 116044,China

Objective Neurodegenerative diseases accompany neuroinflammatory pathological process,during which injury or loss of neurons often *** a result,cognition,learning or movement function is severely *** far,the mechanism concerned is *** C（also called dipeptidyl peptidase,DPPI）,a lysosomal cysteine protease,activates granule-associated serine proteases which play important roles in host reponses to bacterial infection in periphery ***,whether cathepsin C participates in regulation of the process of inflammation in CNS remains *** present study is to explore the role of cathepsin C in CNS inflammatory *** An acute inflammation mice model was established by LPS（25 mg/kg,b.w.） intraperitoneally single *** different time points after LPS injection,the cellular localization,expression pattern and level of cathepsin C was detected by immunohistochemistry and Western *** expression of Cathepsin C mRNA, IL-1βmRNA and TNFa mRNA were studied by in situ hybridization and *** vitro,BV mouse microglia lines were treated with various concentrations of LPS or IL-1B for 6 *** the expression of cathepsin C mRNA and the secretion of cathepsin C were detected by RT-PCR and ELISA,*** activity of cathepsin C was measured by chromogenic substrate *** After LPS injection,the expression of cathepsin C and cytokines in the brain was *** 24 h point,the activated microglia started to express cathepsin C and its expression maintained at the highest *** contrast,cathepsin C was exclusively expressed in neurons at 6 h point after LPS *** vitro,both cathepsin C mRNA expression and cathepsin C protein secretion were increased in LPS or IL-1β-treated BV cells in a dose-dependent *** addition,the activity of cathepsin C was also enhanced after *** The results indicate that cytokines induce the expression and activity of cathepsin C in microglia i

关键词： cathepsin C neuroinflammation cytokine microglia

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Distinctive change in the sensitivity of VTA-NAc dopaminergic pathway to morphine during prolonged withdrawal

Distinctive change in the sensitivity of VTA-NAc dopaminergi...

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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： Lin-Lin SUN,Ling HU,Yi-Jing LI,Cai-Lian CUI~* Neuroscience Research Institute,Peking University,China Department of Neurobiology,School of Basic Medical Sciences,Peking University,China Key Lab for Neuroscience,the Ministry of Education,China and Key Lab for Neuroscience,the Ministry of Public Health,China

Objective Drug withdrawal has been believed to be associated with dysregulation of reward properties, especially the decrease of sensitivity to the drug previously *** present study is designed to determine whether prior opiates exposure altered the rewarding sensitivity to opiates used *** We recorded the dopamine(DA) neuron firing activity in ventral tegmental area(VTA) using the electrophysiological in vivo,tested the level of DA metabolites in nucleus accumbens(NAc) using HPLC,and observed the behavioral sensitivity to morphine-induced reward with conditioned place preference(CPP) ***(1) A significant withdrawal syndrome was observed at 24 h postwithdrawal in chronic morphine-treated rats,which disappeared 7 d later.(2) Electrophysiological recording the firing activity of VTA DA neurons revealed a dramatic change from early to prolonged withdrawal,representing a transition from tolerance to sensitization and then to normal after 45 d of withdrawal.(3) HPLC analyses showed that the contents of DA and its metabolites in NAc decreased for at least 14 d but increased significantly after 30 d postwithdrawal in response to morphine challenge.(4) Measuring the behavioral sensitivity to morphine rewards using conditioned place preference(CPP) paradigm,we found that only 45 d-SW rats displayed significant preference for the morphine-associated environment,and disrupting general dopamine signaling prevented this morphine-induced *** Changed sensitivity of VTA-NAc dopaminergic signaling is probably the underlying mechanism for the morphine-induced reward behavior after spontaneous withdrawal.

关键词： morphine spontaneous withdrawal dopamine neurons electrophysiological recording sensitivity conditioned place preference

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Autophagic dysfunction in amyotrophic lateral sclerosis

Autophagic dysfunction in amyotrophic lateral sclerosis

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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： Xiao-Jie ZHANG,Liang LI,Sheng CHEN,Wei-Dong LE 1 Neurogenomics,Institute of Health Sciences,SIBS,CAS-SJTUSM,Shanghai 200025,China 2 Neurology,Baylor College of Medicine,Houston,TX,USA

Aberrant protein misfolding may contribute to the pathogenesis of amyotrophic lateral sclerosis(ALS) but the detailed mechanisms are largely *** investigate if there is any autophagic alteration in ALS and used SOD1G93A mutant mice,a model of ALS to examined the processings of autophgy related molecules(LC3, Beclin-1,p-mTOR,p62,p-P70,p62,Atg5 and Atgl2 processing) by immunostaining and Western blot in the spinal cord and other central nervous *** have demonstrated that the autophagic protein marker LC3-Ⅱis markedly and specifically increased in the spinal cord motor neurons(MNs) of the ALS *** microscopy and immunochemistry studies have shown that autophagic vacuoles are significantly accumulated in the dystrophic axons of spinal cord MNs of the ALS *** these changes in the ALS mice appear at the age of 90 d when the ALS mice display modest clinical symptoms;and they become prominent at the age of 120 *** clinical symptoms are correlated with the progression of MNs ***,we have found that p62/SQSTM1 is accumulated progressively in the spinal cord,indicating that the possibility of impaired autophagic flux in the SOD1G93A ***,to our surprise,we have found that treatment with autophagy enhancer rapamycin accelerates the MNs degeneration,shortens the life span of the ALS mice,and has no obvious effects on the accumulation of SOD1 *** addition,we have demonstrated that rapamycin treatment in the ALS mice causes more severe mitochondrial impairment,higher Bax levels and greater caspase-3 *** findings suggest that selective degeneration of MNs is associated with the impairment of the autophagy pathway and that rapamycin treatment may exacerbate the pathological processing through apoptosis and other mechanisms in the ALS mice.

关键词： ALS motor neuron degeneration protein aggregation autophagy apoptosis

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Interactions between vl and v4 in processing global visual contours

Interactions between vl and v4 in processing global visual 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： Charles D.Gilbert Lab.Neurobiol Rockefeller Univ.New YorkNYUSA

Objective Integration of local image components into global shapes is crucial for perceiving coherent objects in visual *** studies indicate that V1 is involved in mediating contour integration—a delayed component of neuronal responses in V1 is predictive of perceptual saliency of *** contour-related responses are subject to the influences of attentional control and perceptual learning,which suggests task-dependent gating of contextual interactions in V1 via feedback connections from higher cortical *** To test this speculation directly,we chronically implanted Utah arrays into retinotopically matched regions in macaque V1 and V4,and trained the animal to detect visual contours formed by collinear bars embedded in a background of randomly oriented bars. Results By comparing neuronal activity recorded simultaneously in these two areas in response to the same contour stimuli in the detection task,we could replicate earlier findings in V1(Li et al.,Neuron 2006,2008)—neuronal responses that were strongly correlated with the length of the global contours did not appear until 100 ms after stimulus onset,about 60 ms longer than the response latencies of V1 neurons to the *** contour activated neuronal responses in V4,however,showed a different time *** the response outset,which was on average about 15 ms later than that in V1,neurons in V4 already carried information about contours of different lengths,although the contour-related responses were weaker than those seen in the late components of both V1 and V4 ***, as the contour-related responses evolved with time in these two cortical areas,contour activated responses reached a maximum strength first in V4,about 15 ms earlier than *** Our observations suggest that V4 detects the presence of a global configuration of contours earlier than V1,and that the countercurrent processing via feedforward and feedback connections between lower and higher cortical

关键词： contour integration primary visual cortex visual area 4 timing feedback gating

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The role of Shp2 in fear memory and synaptic function

The role of Shp2 in fear memory and synaptic function

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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 YANG~(1,2),Xun-Yi YAN~(1,2),Wen LU~(1,2),Mao YE~(1,2),Heng AI~(1,2),Jian-Hong LUO~(1,2,*) 1 The Key Laboratory of Medical Neurobiology of Ministry of Health 2 Institute of Neuroscience,School of Medicine, University of Zhejiang,Hangzhou 310058,China

Objective Shp2 is member of the Src homology-2(SH2)-containing protein tyrosine phosphatase (PTPs) *** is widely expressed,with relatively high levels in the brain and *** evidence suggests a critical role of Shp2 in cellular signaling and development of the CNS,but the role of Shp2 in modulating synaptic function is *** we known,mutations in SHP2 gene cause clinically similar but distinctive disorders, LEOPARD syndromes(LS) and Noonan syndromes(NS).Strikingly,most of these patients have a mild mental ***,Shp2 in postsynaptic density protein complex physically associates with NR2B subunit,but the physiological function is *** study is to investigate the role of Shp2 in fear memory and synaptic function. Methods Slice electrophysiological experiment and behavior test were done in both wildtype and forebrain specific Shp2 knockout *** biology,co-immunoprecipition assay,Western blot and cell culture were used in this ***(1) Our data suggest that the fear memory reconsolidation is impaired in the Shp2 knockout mouse;(2) The paired pulse facilitation(PPF) of Shp2 knockout mouse is similar to that of wildtype mouse,but the LTP induction is impaired in Shp2 knockout mouse;(3) Identified a motif of NR2B C-terminus is specifically interacted with Shp2;(4) NMDAR decay time of Shp2 knockout mouse is significantly faster than that of wildtype *** Shp2 is involved in fear memory by regulating NMDAR mediated synaptic function in CNS.

关键词： Shp2 NMDA receptor Leopard syndrome fear memory synaptic function

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Roles of nuclear receptors LXRs and ERs in the neuroprotection of dopaminergic neurons in the midbrain

Roles of nuclear receptors LXRs and ERs in the neuroprotecti...

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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： Wen-Qiong GUO~1,Hong-Liang YI~1,Xiao-Tang FAN~2,Hai-Wei XU~(3,*) 1 Department of Physilogy,Third Military Medical University.Chongqing 400038,China 2 Department of Histology and Embryology,Third Military Medical University,Chongqing 400038,China 3 Southwest Eye Hospital,Southwest Hospital,Third Military Medical University,Chongqing 400038,China

Objective To explore the roles of liver x receptors(LXRs) and estrogen receptors(ERs) in the activation of microglia and astrocyte in the substantia nigra(SN) of the midbrain and its relationship with the degeneration of dopaminergic *** The expression of LXRs subtypes(LXRa and LXRβ) and the ERs subtypes(ERa and ERp) in the midbrain of mice was detected with RT-PCR and ***α-/-,LXRβ-/-,LXRaβ-/- mice,ovariectomy mice and wildtype mice were used in this *** wildtype mice and ovariectomy mice were treated with agonist of LXR TO901317 and 17β-estradiol *** protein levels of ERK and AKt were detected by Western ***(1) Both LXRα,LXRβ,ERa and ERβare expressed in the midbrain of fourmonth old mice,and LXRβis expressed at higher levels than LXRα.Immunohistochemistry confirmed the expression of LXRs and ERs.(2) Compared with age-matched WT mice,microglia and astrocyte were over-activated in LXRβ-/- and LXRαβ-/- mice,of which glia over-activation are more remarkably in the LXRα-/-β-/- *** the number of TH-positive neurons in the SN and TH-ir fiber density in SNpr were decreased in the LXRβ-/-,and extremely reduced in the LXRα-/-β-/- mice.(3) Intraperitoneal injection of LPS to the 4-month-old female WT mice can trigger microglia activation and release inflammatory factors such as IL-1β,IL-6 and TNF-α.LXR agonist TO901317 can effectively block the activation of microglia and reduce mRNA levels of proinflammation factors including IL-1β, IL-6 and TNF-α.(4) The number of TH-IR neurons and the gene expression level of DAT significantly decreased in ovariectomized mice,and treatment with estrogen can prevent the reduction of *** derived neurotrophic factor was involved in the effect of *** By modulating the activation of microglia and astrocyte and their function of pro-inflammatory factors and neurotrophic factors level,both LXRβand ERβproduce neuroprotection effect on dopaminergic neuron

关键词： liver x receptor estrogen receptor dopaminergic neuron microglia astrocyte

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Central sensitization in hypothalamic arcuate nucleus induced by peripheral inflammation

Central sensitization in hypothalamic arcuate nucleus induce...

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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： Jian-Ming PENG,Xiao-Yong LI,Ning-Ang LIU,Wei LI,Long-Sheng XU,Xing-Hong JIANG~* Key Laboratory of Pain Basic Research & Clinical Therapy,Department of Neurobiology and Institute of Neuroscience,Medical College of Soochow University,Suzhou 215123,China

Objective In recent years great progress has been made in the study of central sensitization of nociceptive neurons in the spinal cord,in which the glutamate NMDA receptor plays a pivotal *** less is known about sensitization in the supraspinal centers related to the pain *** aim of this study was to test whether central sensitization can be induced in nociceptive neurons in the hypothalamic arcuate nucleus by peripheral inflammation, which is known to be one supraspinal component of the endogenous pain-modulating *** Peripheral inflammation was induced by plantar injection of complete Freund's adjuvant(CFA)into the hind paw of *** unit neuronal activity was recorded from the arcuate nucleus(ARC)in the slice of mediobasal hypothalamus as well as in anesthetized *** following inflammation was measured by behavioral paw withdrawal responses. The function of NMDA receptor in ARC was detected by Western blot *** receptor antagonists and kinase inhibitors were used to analyze the underlying mechanisms of signal transduction *** Behavioral measurement confirmed a definite hyperalgesia following peripheral *** sensitization was found in ARC as evidenced by(1)significant increase in the frequency of spontaneous unit discharge of ARC neurons from brain slice of inflamed rats,as well as from anesthetized inflamed rats,as compared to the control rats;(2)enhancement of responses of ARC neurons to glutamate and NMDA application in slice of inflamed rats,and the responses of ARC neurons to non-noxious and noxious stimulation in anesthetized inflamed rats were enhanced as ***-regulated expression of phospho-NRl and phospho-NR2B subunit,rather than NR1 and NR2B,was observed in ARC of inflamed ***-ARC microinjection of MK-801(NMDA receptor antagonist),Ro25-6981 (NR2B subunit antagonist),CNQX(non-NMDA receptor antagonist)and PP2(Src protein tyrosine kinase selective inhibitor)cou

关键词： hypothalamic arcuate nucleus central sensitization hyperalgesia NMDA receptor,NR2B subunit Src tyrosine kinase inflammation

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