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Localization of molecular determinants in sensitivity of sodium channels to BmK I probing by surface plasmon resonance assay

Localization of molecular determinants in sensitivity of sod...

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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： Pin YE,Xing-Hua FENG,Hong-Tian YANG,Yong-Hua JI~* Lab of Neuropharmacology and Neurotoxicology,Shanghai University,Shanghai 200444,China

Previously,domain IV S3/S4 linker was demonstrated to be an important region determing the sensitivity of sodium channels to BmK I,a sodium channel-specific site-3 *** the localization of molecular determinants in sensitivity of sodium channels to BmK I remained *** this study,through channel alignment,DIV/S3-S4 linker in BmK I-insensitive rNav1.8 was inserted by two amino acids(LE) compared with *** constructing channel mutants mimicing the rNav1.8 DIV S3/S4 region in rNav1.5 backbone,the sensitivity of rNav.15 mutants to BmK I was remarkably ***,two peptides were synthesized according to the DIV/S3-S4 linker in rNav1.5(peptide P1) and rNav1.8(peptide P2).The binding affinities of peptides to BmK I was investigated by surface Plasmon resonance(SPR).The results showed that both P1 and P2 could bind with BmK *** there were significantly differences in binding capability between these two *** binding response(RU) of the peptide P2 was reduced to about 1/3 of the peptide *** association kinetics of P2 was also *** was presumed that the insensitivity of sodium channels to BmK I could be attributed to the alteration of microstructure of the receptor site by LE ***,it may provide cludes for the diversity of spatial structure of receptor sites mapping for BmK I-sodium channel interaction.

关键词： sodium channels surface plasmon resonance BmK I

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Cpne5,a new Ca2+ dependent phospholipids binding protein,works as a negative factor in the neuronal migration

Cpne5,a new Ca2+ dependent phospholipids binding protein,wor...

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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： Xuefeng DING,Yan WU,Fei WANG,Yongqi ZHAO,Ying WU,Shuhong LIU,Wenhong FAN,Lingling ZHU,Ming FAN Department of Brain Protection & Plasticity Research,Beijing Institute of Basic Medical Sciences,Beijing 100850, China

Cpne5 is a new Ca dependent phospholipids binding *** Previous studies on Cpne5 showed that it was mainly expressed in the ventricular zone（VZ）.Further investigation demonstrated that Cpne5 was expressed both in the neural progenitor cells and newborn neurons in *** indicates that Cpne5 might play an important role in neurogenesis of the ventricular *** confirm our presumption,we established in utero electroporation model. With the shRNA expression vector targeting Cpne5 mRNA,we knocked down Cpne5 expression in the neurocytes in VZ at embryonic day 16（E16d）,and the human GFP-CPNE5 expression vector was transfected into the neurocytes in VZ at embryonic day 16,and then Postnatal mouse brain at 3 days after birth（P3d,6d after electroporation） were fixed with 4%PFA and then sliced at 30μm *** analysis on slices showed that inhibiting Cpne5 expression can remarkably increase the number of neuron migrating to the cortex surface,and overexpressed CPNE5 protein can remarkably decrease the number of neuron migrating to the cortex *** indicates that Cpne5 may work as a negative factor in the neuronal migration.

关键词： Cpne5 neurodevelopment in utero electroporation neuronal migration

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Amygdala neurons encode fear and anxiety

Amygdala neurons encode fear and anxiety

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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： Long-Nian LIN Key Laboratory of Brain Functional Genomics(Ministry of Education and Shanghai),Institute of Brain Functional Genomics,East China Normal University,Shanghai 200062,China

Fear and anxiety both produce similar responses to certain *** is an emotional response to an imprecise or unknown threat,and fear is an affective response to a real threat or *** amygdala has been proposed to play an essential role in the mediation of emotions such as fear and ***,the neural coding mechanisms underlying fear and anxiety in the amygdala are not *** using multi-channel recording techniques,we investigated the neuronal activity in the mouse amygdala responding to various threatening contexts. Here we report that in freely behaving mice,one group of neurons in the basolateral amygdala(BLA) could respond to diverse menaces such as heights and moving *** baseline firing rates of these neurons were remarkably low,about(0.1±0.12) Hz.A subset of these neurons can be selectively activated by fear of *** firing rates increased dramatically[(11.39±0.86) Hz]when mice stayed on an elevated platform(10 cm long,7 cm wide,and 10 cm high);their firing rates could reach 50 Hz when mice fell from a high *** subset of these neurons was sensitive to the movement regardless of other properties of *** neurons could respond to all kinds of moving objects,such as moving toys,shaking hands,and flashing characters on the computer *** firing rates increased significantly to 30-60 Hz when given strikingly different moving *** group of neurons in the BLA fires tonically under anxiety conditions in both open-field and elevated plus-maze *** firing patterns of these neurons displayed a characteristic slow onset and progressively increased firing ***,these firing patterns were correlated to a gradual development of anxiety-like behaviors in the open-field ***, these neurons could be activated by any impoverished environment similar to an open-field;and introduction of both comfortable and uncomfortable stimuli temporarily suppressed the activity of t

关键词： amygdala fear anxiety neural coding

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Meditation training improves attention and the ability of perceiving unexpected objects

Meditation training improves attention and the ability of pe...

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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： Chun-Hong HE~(1,2),Jin-Yan WANG~1,Fei LUO~(1,*) 1 Key Laboratory of Mental Health,Institute of Psychology,Chinese Academy of Sciences,Beijing,China 2 Graduate University of Chinese Academy of Sciences,Beijing 100101,China

Objective Recent studies on meditation revealed that short-term or long-term meditation training could improve *** these studies,participants who attended meditation training could perform better in attention tasks than control *** these attention tasks,participants have already known what the stimuli will present on the ***,the real-world raises a different question:how likely are subjects to notice something salient that they do not expect? For example,a person may fail to see a friend in a cinema when looking for an empty seat,even if the friend is waving,a phenomenon known as 'inattentional blindness'(IB).In the present study,we not only examine whether meditation training can improve the ability of focus attention on expectant stimuli relevant to the task,but also test if meditation training can improve the ability of perceiving unexpected *** The experimental group assigned to 4 days(30-min per day) of meditation practice,the control group got no meditation *** Attention Network Test(ANT) was conducted on participants before(Time 1) and after(Time 2) *** IB task was just conducted on the time ***(1) Compared with time 1,the experimental group showed greater improvement in conflict scores on the Attention Network Test at time *** control group also got improvement in conflict scores(maybe because of practice) at time 2,but it revealed no significant difference compared to that of time 1.(2) In the IB task,62.5%subjects in the experimental group noticed the unexpected *** only 25%subjects in the control group noticed *** Meditation training can improve attention and the ability of perceiving unexpected objects.

关键词： meditation Attention Network Test inattentional blindness

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Vangl2 regulation in a mammalian model for planar polarity

Vangl2 regulation in a mammalian model for planar polarity

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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： Arnaud Giese La Lasvaux Claire Mazzocco Elodie Richard Matthew W.Kelley Nathalie Sans John Brigande Mireille Montcouquiol INSERM U862 Neurocentre MagendiePlanar Polarity and Plasticity groupBordeauxFrance University of Bordeaux France

Vangl2 is one of the central proteins controlling the establishment of Planar Cell Polarity in different tissues and ***,results in both flies and mammals suggest that that the localization of Vangl2 protein to specific intracellular microdomains is crucial for normal ***,the molecular mechanisms that control Vangl2 trafficking within a cell are largely ***,we identify a new binding partner for Vangl2,G-protein signaling-GAIP -interacting protein 1(GIPC1).We show that the central PDZ domain of GIPC1 directly associates with the last 12 amino acids of Vangl2,and that GIPC1,along with the motor protein MyosinⅥ(MyoⅥ),co-localizes with Vangl2 in endosomal *** show that a GIPC1/MyoⅥcomplex regulates the levels of Vangl2 at the plasma membrane. Consistent with this result,high resolution imaging by STED microscopy reveals a depletion of Vangl2 in the proximal membrane of hair cells,a location with a large accumulation of ***,downregulation of GIPC1 in hair cells by shRNA in vitro or in utero leads to hair cell maturation defects,including defects in hair bundle orientation and *** results demonstrate a role for GIPC1 in the regulation of Vangl2 protein within developing hair cells. Moreover,morphological analysis of the effects of depletion of GIPC1 indicates a broader role for this molecule in the development of both stereociliary bundles and planar cell polarization.

关键词： planar polarity inner ear traffic cochlea Van Gogh-like 2

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Myricetin attenuates MPP+-induced cytotoxicity by anti-oxidation and inhibition of MKK4 and JNK activation in MES23.5 cells

Myricetin attenuates MPP+-induced cytotoxicity by anti-oxida...

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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 ZHANG,Ze-Gang MA,Jun WANG,Jun-Xia XIE~* Department of Physiology,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:Physiology,Medical College of Qingdao University,Qingdao 266071,China

Objective Increasing evidence suggests that oxidative stress may be implicated in the degeneration of dopaminergic neurons in Parkinson's disease（PD）,and anti-oxidation has been shown to be effective in PD treatment. Myricetin has been reported to have the biological functions of anti-oxidation,anti-apoptosis,anti-inflammation and *** aim of the present study is to investigate the neuroprotective effect of myricetin on l-methyl-4- phenylpyridinium（MPP）-treated MES23.5 cells and the underlying *** The cell viability was assayed by MTT *** production of intracellular reactive oxygen species（ROS）,mitochondrial transmembrane potential（Δψm） and caspase-3 activation were measured by flow *** mitogen-activated protein kinase （MAPK） kinase 4（MKK4） and c-Jun N-terminal kinase（JNK） activities were tested by Western blot *** The results showed that myricetin treatment significantly attenuated MPP-induced cell loss and nuclear condensation. Further experiments demonstrated that myricetin could suppress the production of intracellular ROS,restore theΔψm,increase Bcl-2/Bax ratio and decrease caspase-3 activation that induced by ***,we also showed myricetin decreased the phosphorylation of MKK4 and JNK caused by *** These results suggest that myricetin protected the MPP-treated MES23.5 cells by anti-oxidation and inhibition of MKK4 and JNK activation.

关键词： Myricetin MPP+ oxidative stress MKK4

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Reference values for amplitude-integrated electroencephalogram in infants from preterm to 3.5 months of age

Reference values for amplitude-integrated electroencephalogr...

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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： Dan-Dan ZHANG~(1,2,*),Yun-Feng LIU~3,Da-Tian YE~2,Yue-Jia LUO~1 1 State Key Laboratory of Cognitive Neuroscience and Learning,Beijing Normal University,Beijing 100875,China 2 Department of Biomedical Engineering,Tsinghua University,Beijing 100084,China 3 Department of Pediatrics,Peking University First Hospital,Beijing 100034,China

Objective Amplitude-integrated electroencephalogram(aEEG)is a valuable tool for the continuous evaluation of functional brain maturation in *** amplitudes of the upper and lower margins of aEEG are postulated to change with maturation and correlate with postmenstrual age(PMA).This study aimed to establish reliable reference values of aEEG amplitudes,providing quantitative guidelines for assessing aEEG maturation in neonates and young *** Normal infants(n=274)with PMAs that ranged from 30 to 55 weeks were divided into ten groups according to their *** 5-min segments were selected from each aEEG to calculate the upper/lower margin and bandwidths of the tracing *** Interobserver agreement was achieved with an overall correlation of *** upper and lower margins of aEEG in both active and quiet sleep clearly rose in infants beyond the neonatal *** bandwidth defined as the graphic distance decreased almost monotonically throughout the PMA range from 30 to 55 *** lower margin of aEEG was positively correlated with PMA, with a larger rank correlation coefficient during quiet sleep(r=0.89)than during active sleep(r=0.49).Conclusion Reference values of aEEG amplitudes were obtained in infants with a wide range of PMA and constitute a basis for the quantitative assessment of aEEG maturation in neonates and young *** normative amplitudes of aEEG margins,especially of the lower margin in quiet sleep,are recommended as reference data for the identification of potentially abnormal aEEG.

关键词： amplitude integrated EEG infant reference values upper and lower margins

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Early-stage epileptogenesis and intervention

Early-stage epileptogenesis and intervention

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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： Sheng-Tian LI School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China

Objective Over 30%of people with epilepsy are not responsive to the treatment even to the best available ***,it is of great theoretical and clinical significance to investigate the mechanisms underlying epilepsy,and to search for effective *** reports have shown that N-methyl-D-aspartate（NMDA） receptors are extensively involved in epilepsy genesis and ***,few studies have focused on the role of extrasynaptic NMDA receptors in ***,in the present study we analyzed extrasynaptic NMDA receptor-mediated currents during the early stage of *** is a fundamental molecule in cells, which has been shown to decrease oxidative and excitotoxic cell death as well as ischemic brain *** the current study,therefore,we also tested the effect of NAD on pilocarpine-induced *** Adult C57BL/6 mice models of pilocarpine-induced epilepsy were established,and hippocampal slices were prepared at 24 h after the onset of status epilepticus（SE）.Changes in synaptic and extrasynaptic NMDA receptor-mediated excitatory postsynaptic currents（NMDA-EPSCs） were recorded in CA1 pyramidal neurons by whole-cell patch clamp technique. On the other hand,NAD or vehicle was *** 1 h after the onset of pilocarpine-induced *** of spontaneous recurrent seizures（SRS） was recorded by EEG recording technique in freely moving mice at two weeks ***（1） There were no significant differences in synaptic NMDA-EPSCs between pilocarpine and control groups in terms of rise time and decay time.（2） The peak amplitudes and rise time of extrasynaptic NMDA-EPSCs were not statistically different between the two groups.（3） Extrasynaptic NMDA-EPSCs decay was significantly faster in the pilocarpine-treated mice.（4） NAD treatment markedly decreases the number of spontaneous epileptiform EEG activity.（5） Histological experiments showed that NAD treatment reduces the brain injury in the pilocarpineinduced e

关键词： epilepsy NMDA receptor extrasynaptic NAD+

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Multiple glial-neuronal dialogues in morphine tolerance:role of P2X7 receptor downstream cascades in the spinal cord

Multiple glial-neuronal dialogues in morphine tolerance:role...

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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： Meng-Ling CHEN~#,Hong CAO~#,Long-Zhen CHENG,Yu-Xia CHU,Yu-Qiu ZHANG,Zhi-Qi ZHAO~* Institute of Neurobiology,Institutes of Brain Science & State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

Objective Morphine is a potent ***,its clinical application is restricted due to morphine *** underlying mechanism is not fully *** are thought to be involved in morphine tolerance, and P2X purinergic receptor（P2XR） has been implicated in neuron- glia communication and chronic pain. This study investigated microglia-expressed P2X receptor（P2XR） and its downstream mechanisms underlying the induction of tolerance to morphine analgesia in *** Behavioral tests,SiRNA,Western Blotting, immunohistochemistry,ELISA and electrophysiology methods were used in this *** Chronic morphine treatment induced morphine tolerance and an increase in the expression of P2XR and IL-18 by microglia,IL-18 receptor（IL-18R） by astrocytes and PKCy by neurons in the spinal cord,respectively,which was blocked by a P2XR antagonist or targeting ***,the release of astroglial D-serine,a ligand for NMDA receptor,was increased by chronic morphine,which was attenuated by the D-serine *** D-serine-mediated presynaptic mechanism may contribute to the potentiation of spinal pain-sensitive neurons by chronic morphine treatment. Conclusion The present study revealed multiple dialogues between glial and neuronal cells via cascades involving P2XRs,IL-18,D-serine,NMDARs and PKCy in morphine tolerance,which may provide novel targets for preventing morphine tolerance.

关键词： morphine tolerance P2X7 receptor IL-18 D-serine PKCy glial-neuronal dialogue

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Membrane insertion of plasmalemmal precursor vesicles(PPV) is mediated by RablO interaction with MARCKS during axonal growth

Membrane insertion of plasmalemmal precursor vesicles(PPV) i...

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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-Hui XU~#,Cai-Yun DENG~#,Yang LIU,Tong WANG,Zhen-Ge LUO~* Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,Shanghai 200031,China

The formation of axons and dendrites and maintenance of the neuron's vastly expanded surface require the continuous addition of new *** axon extension,the coordination of membrane traffic,adhesion to extracellular substrate,and reorganization of the cytoskeleton at the peripheral region of the growth cone mediate the protrusive activity of the axon growth *** we have found the involvement of Rab10 in directional membrane insertion of plasmalemmal precursor vesicles(PPV) during neuronal *** the mechanism of Rab10 action remains *** we report that the myristoylated alanine-rich C kinase substrate(MARCKS) interacts with Rab10 and mediates fusion of PPV to the plasma ***-regulation of MARCKs using siRNA against MARCKS abrogated polarized distribution of Rab10 and prevented neuronal ***, blockade of the interaction between Rab10 and MARCKS by over-expressing the MARCKS domain that mediated the Rab10-MARCKS binding abolished membrane fusion of PPVs,which were labeled with BODIPY-ceramide. Membrane fusion of PPVs was also measured by analyzing the TIRF(Internal Reflection Fluorescence) signals of pHluorin-tagged receptors of axon growth promoting factors - TrkB for brain-derived neurotrophic factor(BDNF) and IGFR for insulin like factor 1(IGF-1).We found that down-regulation of MARCKS or blocking its interaction with Rab10 inhibited the TIRF ***,blocking the interaction between Rab10 and MARCKS inhibited axon growth in vitro and in ***,Rab10 interaction with MARCKS mediates fusion of PPV with the plasma membrane,a process required for axonal growth.

关键词： MARCKS RablO plasmalemmal precursor vesicle axon growth docking fusion

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