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Hydrogen sulfide:a novel neuroprotectant agent to treat neurodegerative diseases

Hydrogen sulfide:a novel neuroprotectant agent to treat neur...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jin-Song BIAN Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore 117597 Singapore

Objective Hydrogen sulfide (H2S) plays a critical role in regulation of brain ***, its impact on neurodegenerative disease is still *** present study was undertaken to investigate the therapeutic effects of H2S on neurodegenerative *** and Results We found sodium hydrosulfide (NaH S)-a donor for H2S, concentration-dependently suppressed rotenone-induced cell apoptosis with MTT and Hoechst 33342 staining *** S prevented rotenone-induced Bcl-2/Bax decrease, mitochondrial membrane potential (AΨm) dissipation, cytochrome c release, and caspase-9/3 ***, NaHS attenuated rotenone-induced p38-and JNK-MAPK *** also examined the protective effect of H2S in Parkinson's disease (PD) animal *** endogenous H2S level was markedly reduced in the SN in a 6-hydroxydopamine (6-OHDA)-induced PD rat *** administration of NaHS (an H2S donor) dramatically reversed the progression of movement dysfunction, loss of tyrosine-hydroxylase positive (TH+)-neurons in the SN and the elevated malondialdehyde level in injured striatum in the 6-OHDA-induced PD model.H2S specifically inhibited 6-OHDA evoked NADPH oxidase activation and oxygen ***, administration of NaHS also prevented the development of PD induced by *** treatment inhibited microglial activation in the SN and accumulation of pro-inflammatory factors (***-α and nitric oxide) in the striatum via NF-κB ***, significantly less neurotoxicity was found in neurons treated with the conditioned medium from microglia incubated with both NaHS and rotenone compared to that with rotenone only, suggesting that the therapeutic effect of NaHS was, at least partially, secondary to its suppression of microglial *** We demonstrate for the first time that H2S may serve as a neuroprotectant to treat and prevent neurotoxin-induced neurodegeneration via multiple mechanisms including anti-oxidative stres

关键词： hydrogen sulfide neurodegenerative diseases Alzheimer' s disease Parkinson' s disease

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Bip overexpression induces tau hyperphosphorylation in HEK293/tau cell

Bip overexpression induces tau hyperphosphorylation in HEK29...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Zan-Chao LIU Jian-Zhi WANG Qing TIAN Department of Pathology and Pathophysiology Key Laboratory of Neurological Disease of National Education Ministry and Hubei Province Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

Objective Alzhermer's disease (AD) is the most common neurodegenerative disease with the progressive cognitive impairment as the major clinical *** microtubule associated protein tau is the major component of intracellular neurofibrillary (NFTs), which is positively correlated with the decline of learning and memory in AD *** upstream effectors leading to tau hyperphosphorylation are still not fully *** reticulum (ER) is responsible for the posttranslational processing of newly synthesized proteins and ensuring proper protein folding and *** of damages (such as oxidative stress) can induce ER stress, which has been shown activated in the AD *** level of Bip, an ER stress marker, was also shown in the temporal cortex and the hippocampus of AD patients compared with age-matched *** present study is to explore whether Bip overexpression could induce tau *** Plasmid of Bip with EGFP-N1 vector was constructed and transfected into HEK293/tau *** phosphorylation levels of tau protein and the activities of the key tau phosphorylation related protein kinase glycogen synthase kinase-3β (GSK-3β), and the key protein phosphatase protein phosphatase 2A (PP2A), were *** (1) Bip overexpression in HEK293/tau cell induced increased phosphorylation levels of tau at Ser214, Ser262, Ser396, Ser404, Thr205 and Thr231 epitopes.(2) The increased phosphorylation levels of GSK-313 at Tyr216 and decreased phosphorylation levels at Ser9 were observed (indicating GSK-313 activation).(3) The phosphorylation of PP2A catalytic subunit at Tyr307 had no significant change.(4)Additionally, we also found increased Bip enhanced the association of tau and GSK3β by *** All these data confirmed that overexpression of Bip could induce hyperphosphotylation oftau in vitro by activating GSK-3β and enhancing the association of tau and GSK3β.

关键词： Bip tau GSK3β

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Designation and evaluation of glial glutamate transporter-1a antisense oligodeoxynucleotides

Designation and evaluation of glial glutamate transporter-1a...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Li-Zhe LIU Min ZHANG Yi-Xian LIU Xin CUI Yu-Yan HU Wen-Bin LI Department of Pathophysiology Hebei Medical University 361 Zhongshan East Road Shijiazhuang 050017 China

Objective The present study was undertaken to design the antisense oligodeoxynucleotides (AS-ODNs) of glial glutamate transporter-1 a (GLT-1 a) and to evaluate the effectiveness of the designed AS-ODNs on the expression of *** Five sequences ofGLT-la AS-ODNs were designed according to the C terminus specific sequences of GLT-la mRNA using antisense design software of IDT *** blot analysis was used to examine the inhibition effect of the 5 GLT-la AS-ODNs on the expression of GLT-la for evaluation of their *** The sequences of the 5 GLT-la AS-ODNs were as follows: P1: 5'-AGCTGACTTTCCATTGGCCGC-3', P2: 5'-GGTT CTTCCTCAACACTGCA-3', P3: 5'-CACGTTTCCAAGGTTCTTCC-3', P4: 5'-TTGGCTGAGAATCGGGTCATT-3', P5: 5'-ATTGGCTGAGAATCGGGTC-3'.Among the above 5 GLT-1a AS-ODNs, the P2 sequence, which could down-regulate the ceftriaxone (Cef)-induced up-regulation of GLT-1 a by more than 70% in rats hippocampal CA1 subfield, showed the most significant inhibition effect on the expression of GLT-la, while it had no effect on the expression of *** P2 sequence could also significantly down-regulate the expression of GLT1a in the hippocampal CA1 subfield of normal rats and rats with cerebral ischemic preconditioning (CIP).Conclusion Among the 5 designed GLT-1a AS-ODNs (P1-P5), the P2 sequence could significantly and specifically inhibit the expression of GLT-1a, which could not only inhibit the basal GLT-1a expression, but also inhibit the Cef-and CIP-induced up-regulation of GLT-1 a expression in the rat hippocampal CA 1 subfield.

关键词： GLT-la AS-ODNs ceftriaxone cerebral ischemic preconditioning hippocampus rat

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A computational model of information processing in retina

A computational model of information processing in retina

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Yi-Yang LI Dan ZHANG Da-Hui WANG Department of Systems Science Beijing Normal University Beijing 100875 China

Objective In the visual system, experiments have shown the physiology of retina and the electrophysiological property of retinal neurons, including the response to proper stimulus and the adaptation to *** a visual object, retina transforms optical signals to electrophysiological signals which are transmitted to downstream neural system by ganglion cells as a ***, the overall features of efferent signal from ganglion cells are not very ***, we build a computational model of the retina based on the model by Momiji and the physiological structure of *** model includes the ON and OFF pathways which can be used to simulate the information processing in retina and investigate the overall features of retina efferent *** The model contains basic types of retinal neurons, i.e., photoreceptor cell (RC), horizontal cell (HC), bipolar cell (BC), amacrine cell (AC) and ganglion cell (GC, includes MGC and PGC).The ON and OFF pathways start from *** ratios between each type of neurons obey RC∶ HC∶ BC∶ AC∶ MGC∶ PGC=25∶25∶6.25∶6.25∶4∶*** are placed on a 2-dimensional *** HC receives excitatory synaptic afference from 4 adjacent RCs and forms electrical synapses with 8 adjacent *** ON-type BC receives inhibitory synaptic afference from 8 adjacent RCs while each OFF-type BC receives excitatory synaptic afference from 8 adjacent *** AC receives excitatory synaptic afference from 1 BC and feed back to it, each MGC receives excitatory synaptic afference from 8 adjacent BCs while each PGC receives excitatory synaptic afference from 3 adjacent *** use a set of differential equations to describe the cascade reaction after photon reaching RC, including the concentration of [PDE] increasing, [cGMP] hydrolyzing, cationic channels closing, the intracellular concentration of Ca2+ and H+ decreasing, and finally RC *** membrane potential of HC, BC and AC are described as differential *** GC, action

关键词： retina neural network computational model

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The development of neural microcircuits in mouse neocortical layer 1

The development of neural microcircuits in mouse neocortical...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Yong-Chun YU Yinghui FU Laboratory of Development of Neural Synaptic Microcircuit Institute of Neurobiology Fudan University Shanghai 200032 China

Objective Layer i is the most distinct and characteristic lamina of the cerebral *** the neocortex develops, layer 1 populated by two basic neuronal cell types, Cajal-Retzius (C-R) cells and *** many studies strongly showed that the neurons in layer 1 have the important roles for the neocortical development and integrating inputs from high order cortical and thalamic areas, yet the developmental neural microcircuits of layer 1 neuron remain poorly *** Here we studied the development neural microcircuits in the layer 1 using multiple patch clamp recording and neurobiotin *** From P1 to P7, we observed that electrical coupling interconnected around 14% between interneurons and 19% between C-R *** also found the chemical synaptic connections between layer 1 neurons were rather low around the first postnatal week; it increased dramatically around the second postnatal *** P8, two types of interneuron characterized by action potentials, the late spike (LS) and the bursting nonadapting (bNA), were *** 68% of the cells we recorded were LS cells which the dendrites and the very dense local axonal field were confined primarily to layer 1; 22% of the bNA cells were multipolar neurons with axons descending out of layer *** found that LS cells were interconnected by electrical coupling (87%), whereas electrical coupling between bNA cells was infrequent (5%).We also found that the electrical coupling mediated synchronizations of the spontaneous activities were 34.5% between LS cells and only 1% between bNA *** addition to the chemical synapse, we observed that bi-directional GABAergic synaptic connections were widely populated between the LS cells (57%), and only 4% between bNA *** chemical synaptic direction between LS cells and bNA cells was uni-direction, and was mostly from LS cells to bNA *** We showed the developmental microcircuits between two types of GABAergic neur

关键词： development microcircuits interneuron layer 1 neocortex

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Myosin X is required for the migration of cortical neurons through regulating cytoskeleton

Myosin X is required for the migration of cortical neurons t...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Xing-Da JU Ye GUO Hua-Li YU Yu-Ting LI Xiao-Juan ZHU Laboratory of Neural Plasticity Key Laboratory of Molecular Epigenetics of Ministry of Education Institute of Cytology and Genetics Northeast Normal University Changchun 130024

Objective Cortical development is an important process during the establishment of nervous *** generation of cortical layers relies on the proliferation, differentiation, migration and projection of cortical neurons with an inside-out mode, and nearly all these processes are closely related with the regulation of *** X (Myo X), an untraditional member of myosin families, was found to interact directly with both microfilaments and microtubules, and had been identified as a functional factor during nerve cells migration of Xenopus and *** has previously shown that Myo X is highly expressed during brain development, however, little is known of the role that Myo X is required for neuronal migration in cerebral *** we report that Myo X promotes neuronal migration by regulating the dynamics of *** Firstly, we analyzed the expression pattern of Myo X in the developing cortex with in situ hybridization and immunohistochemistry ***, to determine the function of Myo X in the expressed area, in utero electroporation was performed with Myo X miRNA at E 15.5 and brains were analyzed at E 18.5, a period of time when neuronal migration is ***, to further explore the mechanism that Myo X regulates neuronal migration, we cultured neurons from electroporated *** (1) Myo X is mainly expressed in the VZ, SVZ and IZ zones.(2) Knocking down the expression of Myo X resulted in a migration defect in the cortical plate, which was caused by morphological changes of migrating neurons, cells lacking Myo X failed to adopt the bipolar morphology that Myo X-expressing cells acquired.(3) Being the same as the morphological analysis in vivo, cells lacking Myo X have changed dynamic regulation of *** Our data suggested that Myo X mediated neuronal migration by regulating cellular morphology through modulation of the cytoskeleton dynamics.

关键词： cortical development neuronal migration Myosin X cytoskeleton dynamic

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Delayed De Novo hippocampus synthesis of PKMζ determines long term memory retention

Delayed De Novo hippocampus synthesis of PKMζ determines lo...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jian-Feng LIU Lin LU National Institute on Drug Dependence Peking University Beijing 100191 China

Objective Long term memory formation requires several signaling pathways activation and protein synthesis after learning, which is called *** classical opinion of the time-window of consolidation is approximately 6 hours, after which the newly formed memory transfers to be a stable long term *** lots of studies suggested that another protein synthesis-dependent phase happened later than consolidation, might determine the retention of long term *** evidences show that protein kinase Mζ (PKMζ), atypical kind of protein kinase C, play a critical role in the maintenance of long term *** a hippocampus (Hip)-dependent memory, contextual fear memory is a commonly used memory model, but the underlying molecular mechanism and role of Hip in memory retention are still not completely *** present study is to explore the role of PKMζ *** retention of contextual fear *** The total PKMζ alteration was tested by Western Blot assays and Immunohistochemistry at the different time points after contextual fear *** term memory was evaluated at the 10th day *** PKM inhibitor peptide was bilaterally intracranial microinjected to dorsal Hip at different time points to determine the role of PKMζ in the *** (1) The expression of PKMζ increased after 12 h following contextual fear conditioning but not 3 h, 6 h or 9 h after conditioning, and the effect endured to additional 12 h at least.(2) 12 h post-conditioning inhibition of PKMζ in dorsal Hip selectively impaired dayl 0 memory (tested on 10th day after conditioning) but not day2 memory.(3) Inhibit PKMζ immediately after contextual fear conditioning did not disrupt long term memory formation and *** Delayed synthesis of PKMζ in hippocampus after conditioning determines the retention of long term contextual fear memory.

关键词： fear memory long term memory PKMζ protein synthesis memory retention

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Simultaneous neural ensemble recordings of pain in the cerebral cortex of behaving rats

Simultaneous neural ensemble recordings of pain in the cereb...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jun CHEN Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders Tangdu Hospital Fourth Military Medical University Xi ''an 710038 China Institute for Biomedical Sciences of Pain Capital Medical University Beijing 100069 China

Objective In the past 10 years, a technique allowing simultaneous, multisite and many neuron recordings in freely moving and behaving animals (e.g., monkeys, rats and mice) and even in human subjects has been well developed and successfully applied in many regions of the *** state-of-the-art technique of in vivo simultaneous multisite recordings of neural ensemble responses in the brain enables a good combination with various behavioral assays in freely moving and behaving *** this report, Ⅰ would like to introduce the use of this technique in study of pain in the cerebral cortex of behaving *** Microwire electrode arrays (2×4 or 2×8) were implanted into the target brain area of a rat in the aid of stereotaxic surgical *** at least 7 days of recovery, simultaneous recordings of cerebral cortical neural ensemble responses in a behaving rat were carried out using the Plexon multichannel Acquisition Processor (MAP) system and an overhead video tracker system processed by Plexon CinePlex software that enables continuous real-time behavioral tracking and synchronization of video and neural signals through interaction with the MAP system.A Plexon MAP system receives and processes the pre-amplified and filtered neural ensemble signals by RASPUTIN Software for online displaying, sorting, recording and synchronizing of the neural ensemble *** nociceptive stimuli, including mechanical, thermal and chemical modalities, were applied to the rat's *** Long-term unitary stability was confirmed by various statistical *** neuronal units were identified by online or offline sorting from the primary somatosensory (S1) cortex and the motor cortex (MCx).The neuronal units identified in the S 1 area were wide-dynamic-range (WDR) and nociceptive-specific (NS) in nature, while those in the MCx were also responsive to noxious *** neural ensemble responses can be significantly changed by periphera

关键词： simultaneous neural ensemble recordings pain cerebral cortex behaving animals

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NMDA-receptor antagonist MK-801 attenuates MMN-like responses in both awake and anesthetized rats

NMDA-receptor antagonist MK-801 attenuates MMN-like response...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Ying-Ying LIU Ning WANG Jin-Yan WANG Fei LUO Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences Beijing 100101 China Graduate University of Chinese Academy of Sciences Beijing 100101 China Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences Beijing 100101 China

Objective Schizophrenia patients always have significant attenuated mismatch negativity (MMN) response, which reveals a deficient cognitive process precision on pre-attentive sensory *** in NMDA receptor system are supposed to mediate the MMN attenuation on schizophrenia ***, there are few studies on MMN response in animal schizophrenia model, especially on awake ***, this study is aimed to explore the proper condition to evoke MMN responses in both awake and anesthetized rats, compare MMN responses under different consciousness states, and estimate whether the NMDA receptor antagonist MK-801 could block the MMN *** Auditory evoked potentials were recorded during odd ball paradigm, in different states (awake, anesthetized), drugs (saline, low dose MK-801, high dose MK-801) and inter-stimulus intervals (ISI) (1000 ms, 2000 ms, 3000 ms).Results (1) MMN response in awake rats presented two negative components which peaked at 50 ms and 120 ms ***, in the anesthetized rats, the MMN response was one positive slow wave happened during 150-350 ms.(2) Compared with the saline injection, both the low-dose and high-dose MK-801 injection could significantly attenuate the MMN responses in the two states.(3) MMN responses had a significantly lager amplitude at the 3000 ms ISI both during the awake and anesthetized states, compared with the 1000 ms and 2000 ms *** MMN response could be estimated in both awake and anesthetized *** NMDA receptor antagonist MK-801, which suggested a temporary schizophrenia simulation, could attenuate the MMN response.

关键词： schizophrenia MMN NMDA receptor MK-801

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Reversal learning in radial-arm maze training possibly interferes with latent inhibition of adult rats

Reversal learning in radial-arm maze training possibly inter...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Qiang GU Bang-An WANG Meng-Ya WANG Cell electrophysiology Laboratory Wannan Medical College Wuhu 241002 China

Objective Latent inhibition (LI) denotes that a prestimulus with repeated presentation but without reinforcement (***-expose) will interfere with the subsequent learning task related with this stimulation and its change is one important manifestation of *** work aims to explore whether behavioral training of reversal learning could interfere with LI of adult *** Twenty adult male Sprague-Dawley rats (body weights; 100-120 g each) were randomly divided into two groups, pre-expose group (PE) and non pre-expose group (NPE).The experimental protocol includes 3 stages: First, Gemini avoid system was used to observe LI phenomenon of rats, in which the number of active avoidance, no response, and avoiding latency were detected by the *** LI test procedure contained adaptation phase, pre-expose phase, and conditioning ***, the followed intervention training of reversal learning was conducted in the Habitest radial-arm maze system (8 arms).The process included adaptation phase, acquisition phase, and reversal learning phase, in which correct percent of running into arms of rats were ***, after the training of reversal learning, LI was tested in the same approach once *** (1) In the first LI test, the difference of no response number, and the avoiding latency was statistically significant (two-sample t test, P < 0.05) between the PE and NPE groups, while the difference in the number of active avoidance was not significant (P > 0.05).These results mean that PE group shows latent inhibition.(2) In the intervention training of radial-arm maze, the difference in correct percentage of running into arms in two groups at the final day of acquisition phase (A8 day) and the first day of reversal learning phase (R1 day) was significant, respectively (paired t-test, P < 0.001), indicating the occurrence of the reversal learning.(3) In the second LI test, the number of active avoidances or no responses, and avoidin

关键词： latent inhibition reversal learning schizophrenia

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