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Mithramycin A protects neurons from apoptosis via transcriptional inhibition of two BH3-onIy proteins:Bim and Dp5/Hrk

Mithramycin A protects neurons from apoptosis via transcript...

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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： Qiao-Ying HUANG~(1,2),Bo XIE~(1,2),Ming-Tao LI~(1,2,*) 1 Department of Pharmacology,2 Proteomics Center Zhongshan School of Medicine,Sun Yat-sen University,74 Zhongshan RoadⅡ,Guangzhou 510080,China

Mithramycin A,a clinically approved antitumor antibiotic,has been demonstrated to have neuroprotective effects in many different paradigms of neuronal ***,the neuroprotective mechanism of mithramycin A remains to be *** we found that,in the activity deprivation-induced apoptosis of cerebellar granule neurons,mithramycin A protected neurons from apoptosis and inhibited the transcriptional increases of 2 proapoptotic BH3-only proteins Bcl-2 interacting mediator of cell death(Bim) and death protein 5/harakiri(Dp5/Hrk).Either of them has been reported to play a critical role in neuronal apoptosis by us and *** A reversed the dramatic increases of promoter activity and mRNA level of both Bim and Dp5 in a dose-dependent *** also blocked the induction of Bim protein in neuronal apoptosis,despite the fact that we failed to detect endogenous Dp5 ***,mithramycin A had no effect on neuronal apoptosis triggered by overexpression of either Bim or Dp5 *** findings suggest that mithramycin A may exert its neuroprotective effect through inhibiting the transcriptional expression of Bim and Dp5,further supporting mithramycin A as a promising drug for neuroprotection.

关键词： neuroprotection mithramycin A Bim Dp5 cerebellar granule neurons

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Rolipram inhibits the heroin-seeking behavior induced by heroin priming or heroin-associated conditioned cues in rats

Rolipram inhibits the heroin-seeking behavior induced by her...

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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： Miao-Jun LAI~1,Hua-Qiang ZHU~1,Dan FU~1,Wei-Sheng CHENG~1,Han-Ting ZHANG~(2,*),Wen-Hua ZHOU~(1,*) 1 Laboratory of Behavioral Neuroscience,Ningbo Addiction Research and Treatment Center,School of Medicine, Ningbo University,China 2 Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology,West Virginia University Health Sciences Center,USA

Objective Several lines of evidence have suggested a critical role for CREB activities,which activated by changes of cAMP in mediating the rewarding and reinforcement effects of many drugs of *** of phosphodiesterase(PDE) increase the concentration of cAMP and activate the ***,a cAMP-selective phosphodiesterase 4(PDE4) inhibitor has been thought to enhance the cognitive function,but whether the rolipram inhibit the drug seeking behavior is still *** Our aim was to investigate the effect of rolipram,on cueor heroin-primed heroin-seeking in *** were self-administered heroin for 12 days and extinguished for 12 days, then,conditioned cues or heroin priming(250μg/kg) was introduced for the reinstatement of heroin-seeking behaviors. Results The reinstatement of heroin seeking induced by cues or heroin priming was attenuated by administration of rolipram(0,0.3,1 or 3 mg/kg,i.p.) in a dose-dependent *** pretreatment with rolipram did not inhibit the heroin *** expression of p-CREB in nucleus accumbens was increased when pretreatment with *** The data suggested that rolipram could be used as a potential pharmacotherapeutic agent to reduce drug-seeking.

关键词： cognitive enhancer addiction heroin cAMP

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Metallothioneins regulate sensory integration through influencing the functions of interneurons in nematode Caenorhabditis elegans

Metallothioneins regulate sensory integration through influe...

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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： Yin-Xia LI,Yan-Fen ZHANG,Da-Yong WANG~* Key Laboratory of Developmental Genes and Human Disease in Ministry of Education,Medical School of Southeast University,Nanjing 210009,China

Metallothioneins(MTs) have the potential to a variety of physiological processes,including neurobehavioral development,and cognitive *** we further show that MTL-1 and MTL-2,metallothionein proteins, participate in the sensory integration control in Caenorhabditis *** mtl-1 and mtl-2 mutants showed deficits in the integration of two sensory signals,and normal associative learning *** over-expressing MTL-1 and MTL-2 exhibited the similar phenotype of sensory integration to ***-1 and MTL-2 are not necessary for the development of nervous system,but they may function in the regulation of mature neuronal ***, besides exclusively expressing in intestinal cells,expressing MTL-1 and MTL-2 in nervous system and AIY interneurons rescued the sensory integration deficits in mtl-1 and mtl-2 mutants,*** of mtl-1 and mtl-2 decreased the integration of sensory signals in mutants of hen-1 and ttx-3,which are required to regulate the sensory integration in AIY ***,expression of MTL-1 and MTL-2 partially rescued the interaction deficits in hen-1 and ttx-3 ***,MTs may regulate sensory integration in the mature neuronal circuit though influencing the functions of interneurons.

关键词： metallothionein sensory integration AIY interneuron Caenorhabditis elegans

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Ubiquitin self-aggregation and interaction with α-synuclein

Ubiquitin self-aggregation and interaction with α-synuclein

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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： Makoto Hashimoto Department of Chemistry and Metabolism Tokyo Metropolitan Institute for NeuroscienceTokyo 183-8526Japan

＜正＞Objective Parkinson’s disease（PD） and dementia with Lewy bodies（DLB） are characterized by the accumulation of abnormal a-synuclein and ubiquitin in protein aggregates conforming Lewy bodies and Lewy *** proteinaceous intracellular aggregates may contribute to subsequent dopaminergic neurodegeneration. The a-synuclein is a natively unfolded protein that is capable of self-aggregation to form both oligomers and fibrillar polymers with amyloid-like *** is an extremely conserved,8.5 kD,76 residue protein found in all *** has multiple functions but it is primarily involved in a pathway that regulates the bulk of intracellular protein *** demonstrates that ubiquitin plays an important role in alpha-synuclein ***,the feature and mechanism among ubiquitin and synuclein proteins in neurodegeneration are not *** present study is to investigate the characteristic of ubiquitin and interaction with *** The aggregation features and the interaction between ubiquitin and synuclein was identified by immunobloting and morphological *** （1） Ubiquitin protein is aggregated and fibrillated under certain conditions,i.e.,increasing time lag,high temperature, low pH and ferrous iron oxidation in vitro.（2）α-Synuclein WT appears bamboo-like longer fibril,while ubiquitin looks thin twisted thread,and can fuse and hybrid with a-synuclein filaments by immunoelectron microscopy assay. （3） In stable synuclein B103 neuroblastoma cells,ubiquitin colocalized with synuclein in inclusion bodies and could accumulate and ubiquitinate with synuclein in certain *** These results suggest that ubiquitin could self-aggregate and might interact with a-synuclein in neurodegeneration.

关键词： ubiquitin synuclein aggregation neurodegeneration dementia with lewy bodies（DLB）

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ost-operative cognitive dysfunction is correlated with urine formaldehyde level in elderly noncardiac surgical patients

ost-operative cognitive dysfunction is correlated with urine...

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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： Tao SU,Rong-Qiao HE~* Institute of Biophysics,CAS

Objective It has been shown that accumulation of endogenous formaldehyde can lead to human cognitive impairment and memory loss in *** purpose of this study is to assess cognitive outcome in elderly noncardiac surgical patients and to investigate the correlation between endogenous formaldehyde level and postoperative cognitive *** We studied ninety-five elderly patients aged between 65 and 80 who were undergoing major orthopedic surgery or abdominal *** day before and one week after the surgery,all patients were subjected to a neuropsychological *** samples were obtained one day before surgery and on day 1,day 2 and day 7 after *** of urine formaldehyde for all enrolled patients were analyzed by high-performance liquid *** formaldehyde concentration after surgery divided by that before surgery was used as a ratio([FA]/[FA]) to assess changes in endogenous *** Ninety-five patients were included in the study and 30(31.6%) were diagnosed with *** urine formaldehyde level of all patients with and without POCD increased markedly on day 1 and day 2 after *** urine formaldehyde level from baseline (before surgery) of patients with POCD was significantly higher(n = 30,P<0.01) than patients without POCD (n = 65);and strikingly,the ratio[FA]/[FA] was significantly greater(n = 30,P<0.001) on day 7 after surgery. Conclusion Levels of urine formaldehyde were elevated under the stress of surgery,and the increase on day 7 may provide a new marker for diagnosing POCD.

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Local neural population activity pattern "gamma oscillation" under visual functional development of awake mouse primary visual cortex

Local neural population activity pattern "gamma oscillation"...

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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： Guang CHEN,Xiao-Hui ZHANG~* Institute of Neuroscience,Chinese Academy of Science,Shanghai 200031,China

The circuits and neural activity patterns underlie the ocular dominance plasticity are not fully *** use the awake mouse visual cortex as the model system to explore this *** the multi-channel electrophysiological recording method we can observe the neural population activity of the visual cortex along the development and under different visual *** recent experiment results show that the awake mouse visual cortex has different states,one is "active" state,and the other is "quiet sleep-like" state with slow/theta *** different local brain states the visual responses are different from the view of the local field potential's *** grating visual stimuli can evoke gamma band oscillation but the frequency band is changing follow the stimulation onset and also different under the two local brain *** gamma oscillation has been thought to be related to some higher brain function and also visual *** phenomenon may play an important role in the neural information *** evidences show that neuronal membrane potential oscillation will affect the plasticity efficiency and ***,we propose that the gamma oscillation will play a role in the visual functional development and *** will provide us a chance to better understand functional development and plasticity from the view of local neural population activity.

关键词： neural population activity patterns synchronization and Gamma oscillation development and plasticity awake mouse

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Examination of MMP9 in cortical lesions from patients with malformations of cortical development

Examination of MMP9 in cortical lesions from patients with m...

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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： Song LI~1,Si-Xun YU~1,Hai-Feng SHU~1,Chun-Qing ZHANG~1,Qing YIN~2,Hui YANG~(1,*) 1 Department of Neurosugery,Xinqiao Hospital,Third Millitary Medical University,Chongqing 400037,China 2 Department of Rehabilitation,Southwest Hospital,Third Millitary Medical University,Chongqing 400038,China

Objective In focal cortical dysplasia typeⅡb(FCDIIb) and tuberous sclerosis complex(TSC), malformative cortical lesions in the cerebral cortex cause epilepsy and other neurological ***, the mechanisms of epilepsy in FCDIIb and TSC remains largely *** evidences indicate that Matrix metalloproteinase 9(MMP9) may be closely involved in *** this study,we investigated whether MMP9 might be involved in malformations of cortical development(MCDs) associated with *** We analyzed the expression and activity of MMP9 in FCDIIb lesions(n = 9) and TSC tubers(n = 13) and in control cortex(CTX, n = 8) by *** methods are used for the specific cellular distribution of MMP9. Results Elevation of protein levels and overactivity of MMP9 were observed in FCDIIb and TSC lesions versus *** studies indicated that MMP9 was strongly characteristically expressed in misshappend cells,namely,hypertrophic neurons,dysmorphic neurons,balloon cells and gaint *** immunofluorescent staining indicated that the reactive astrocytes,not the microglia,highly expressed *** These results suggest that overexpression and overactivity of MMP9 may contribute to the epileptogenesis of FCDIIb and TSC.

关键词： epilepsy Matrix metalloproteinase 9 focal cortical dysplasia tuberous sclerosis complex

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TNF-α mediates hyperalgesia and allodynia by upregulating p-NR1 expression in spinal cord in rats

TNF-α mediates hyperalgesia and allodynia by upregulating p...

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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： Feng GAO,Xin ZHAO,Ce ZHANG,Yu ZHANG~* Department of physiology,Key laboratory of cellular physiology,Shanxi medical university,Taiyuan 030001,China

Objective Following the input of peripheral nociceptive information,some proinflammatory cytokines from microglia,such as TNF-α,will be released,and further produce and maintain the hyperalgesia and allodynia. However,its mechanism is not yet *** is a necessary subunit of NMDAR,and it's well known that phosphorylation of NRl(p-NRl) can upregulate the plasticity of synaptic transmission,which is the essentials of hyperalgesia and *** consequence,the present study was undertaken to determine whether TNF-αcan mediate hyperalgesia and allodynia by upregulating spinal p-NRl expression in *** The paw withdrawal latency(PWL) test for assessing hyperalgesia / allodynia and Western blot for measuring p-NRl were implemented in the models of CFA-induced peripheral inflammation hyperalgesia or in the rats of TNF-αagonist intrathecally ***(1) Thermalgia responses and spinal p-NRl expression will be upregulated in the models of CFA-induced peripheral inflammation pain,which can be alleviated by TNF-αantagonist;(2) Intrathecal administration of TNF receptor(TNFR1) agonist will induce the development of hyperalgesia / allodynia,and enhance the expression of p-NRl in normal rats,which also can be prevented by TNF-α*** TNF-αmediates hyperalgesia and allodynia by upregulating p-NRl expression in spinal cord in rats.

关键词： TNF-α p-NR1 hyperalgesia allodynia spinal cord

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EGF enhances the migration of cancer cells by up-regulation of TRPM7

EGF enhances the migration of cancer cells by up-regulation ...

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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： Hai-Xia GAO,Hai-Lin ZHANG Department of Pharmacology,Hebei Medical University,Shijiazhuang 050017,China

Ion channels are involved in the migration of tumor cells that is required for their invasion and metastasis. In this present study,we describe the role of TRPM7 channel plays in the migration of A549 lung cancer *** TRPM7 currents in A549 cells were first characterized by using means of electrophysiology,pharmacology and RNA interference,and the expression of TRPM7 in A549 cells were also confirmed in mRNA and protein levels. TRPM7 currents in A549 cells have characteristics similar to that of TRPM7 currents reported,with strong outward rectification and sensitive to the inhibition of internal and external divalent *** growth factor(EGF),an important player in cancer development,greatly enhanced the migration of A549 cells and at the same time markedly up-regulated the expression of TRPM7 protein and the current amplitude of *** of TRPM7 function with RNA interference or pharmacological agents no only reversed the EGF-enhanced migration of A549 cells but also inhibited the basal migration of A549 cells in the absence of added ***,the EGF-induced reorganization of cytoskeleton of A549 cells was also prevented by blocking of TRPM7 *** it seems that TRPM7 plays a pivotal role in the migration of A549 cells and TRPM7 could be a potential therapeutic target in lung cancers.

关键词： TRPM7 EGF lung cancer migration

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Effects of NMDA and AMPA receptors in the hippocampal CA1 region during learning-dependent LTP in conscious rats

Effects of NMDA and AMPA receptors in the hippocampal CA1 re...

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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： Shi WANG~1,Jun WANG~1,Dan WANG~1,Cheng-Xi WEI~2,Qing-Hua JIN~(1,*) 1 Department of Physiology and Pathophysiology,Yanbian University Medical College,Yanji 133002 China 2 Institute of Neurosurgery,Affiliated Hospital of Inner Mongolia Nationality University,Tongliao 028007 China

Hippocampus is one of the important sites for mammalian learning and memory,and Long-term potentiation (LTP)is a potential neurophysiological mechanism responsible for learning and *** several in vitro studies indicate that glutamate(Glu)and it's ionotropic receptors involved in the hippocampal LTP,however,little is known about the underlying neurophysiological mechanisms of hippocampal learning-dependent LTP in conscious and freely moving *** this work,glutamate receptor antagonists MK-801and CNQX were locally microinjected into the hippocampal CA1 region,then the extracellular concentration of Glu and amplitude of the field excitatory postsynaptic potential(fEPSP)-LTP in CA1 region were measured during the period of establishment and experimental extinction of the conditioned reflex in conscious rats.

关键词： hippocampal CA1 region learning-dependent LTP ionotropic glutamate receptors conscious rats

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