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Sigma-1 receptor mediates the effect of cyproheptadine on theⅠK in mouse cortical neurons

Sigma-1 receptor mediates the effect of cyproheptadine on th...

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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： Yan-Lin HE,Chun-Lei ZHANG,Xiao-Fei GAO,Jin-Jing YAO,Chang-Long HU,Yan-Ai MEI~* Institutes of Brain Science,School of Life Sciences and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200433,China

Cyproheptadine is a histamine- and serotonin- receptor antagonist,and its effects are observed in the modulation of multiple intracellular signals in previous *** demonstrate here that intracellularly delivered cyproheptadine increased the delayed rectifier outward potassium current（I） by reducing the intracellular levels of phosphorylated PKA in mouse cortical ***-receptor binding assay indicated that cyproheptadine bound to sigma-1 receptor and mediate the cAMP/PKA *** to the sigma-1 receptor mimicked effects of CPH and knock down this receptor abolished the effects of CPH on *** of G eliminated the cyproheptadine-induced effect on I and PKA activity.K2.1α-subunit blocker reduced cyproheptadine-induced effect on I in mouse cortical ***,CPH also enhance the K current when expressed the K2.1α-subunit on HEK293 *** reveal for the first time that CPH enhances I by a sigma-1 receptor-dependent mechanism and selective targeting of the K2.1α-subunit. This result may help to explain some of the uncharacterized effects of CPH on neuron excitability and contribute to the understanding of CPH as more than just a competitive inhibitor of the histamine H and serotonin receptors.

关键词： sigma-1 receptor cyprohetadine IK K_γ2.1α-subunit cAMP/PKA pathway cortical neurons

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Characterization of monoaminergic neurons in the pretectum of zebrafish larvae

Characterization of monoaminergic neurons in the pretectum o...

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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： Shu-Yi ZHANG,Xiao-Quan LI,Jiu-Lin DU Laboratory of Sensory Integration and Behavior,Institute of Neuroscience,Chinese Academy of Sciences,Shanghai 200031,China

The pretectum,one of the arborization fields of retinal ganglion cells,locates in the dorsal-medial *** the preventricular pretectum,there are monoaminergic neurons which axons project to the neuropil of the ipsilateral optic *** on toads and salamanders indicate that the pretectum may be involved in prey discrimination and avoidance ***,it still remains largely unknown how pretectal monoaminergic neurons regulate prey-relevant information processing in the retinotectal pathway in the optic *** electrical stimulation of the pretectum decreased field potentials in the optic tectum of toads,we propose that the pretectum may play an inhibitory role in the retinotectal pathway via monoaminergic *** test this hypothesis,we need to find anatomical evidence showing that pretectal neurons send their axon to the optic tectum and functional evidence showing that pretectal neurons can exhibit different response patterns evoked by prey-like and prey-unlike visual cues. Using immunostaining and Kaede-based photo-conversion in vivo imaging,we first found that some monoaminergic neurons in the pretectum send processes to the deep layer of tectal *** vivo whole-cell recording and extracellular recording were then made on those monoaminergic *** found that those pretectal neurons showed different subtypes of responses evoked by flash and dimming *** characterization of the input and output of those neurons will be performed at both anatomical and functional levels.

关键词： zebrafish pretectum optic tectum monoaminergic prey capture

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HDAC6 regulates aggresome-autophagy degradation pathway of α-synuclein in response to MPP+-induced stress

HDAC6 regulates aggresome-autophagy degradation pathway of ...

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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： Min SU~(1,2),Ji-Jun SHI~1,Ya-Ping YANG~(1,2),Jun LI~2,Yan-Ling ZHANG~1,Jin CHEN~2,Li-Fang HU~2,Chun-Feng LIU~(1,2) 1 Department of Neurology,Second Affiliated Hospital of Soochow University,Suzhou,China 2 Institute of Neuroscience,Soochow University,Suzhou,China

Increasing evidence suggests that the ubiquitin-binding histone deacetylase-6（HDAC6） plays an important role in the clearance of misfolded proteins by *** this study,we treated PC-12 cells overexpressing human mutant（A53T）α-synuclein（α-syn） and SH-SY5Y cells with *** was found that HDAC6 expression significantly increased and mainly colocalized withα-syn in the perinuclear region to form aggresome-like ***6 deficiency blocked the formation of aggresome-like bodies and interfered with the autophagy in response to MPP-induced ***,misfoldedα-syn accumulated into the nuclei,resulting in its reduced clearance,and finally, the number of apoptotic cells significantly *** together,HDAC6 participated in the degradation of MPP-induced misfoldedα-syn aggregates by regulating the aggresome-autophagy *** the mechanism may disclose potential therapeutic targets for synucleinopathies such as Parkinson disease.

关键词： HDAC6 a-synuclein aggresome autophagy MPP+ Parkinson disease

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MicroRNA ablation affects Bergmann glial morphology and disrupts tissue morphogenesis in the developing mouse cerebellum

MicroRNA ablation affects Bergmann glial morphology and disr...

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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： Q.Richard LU Department of Developmental Biology University of Texas Southwestern Medical CenterDallasTX 75390USA

MicroRNAs(miRNAs) play important roles during development of the central nervous system(CNS). Several reports indicate that tissue development and cellular differentiation in the developing forebrains are disrupted in the absence of ***,miRNA functions during cerebellar development have not been systematically *** we conditionally knockout Dicer gene under the activity of human glial fibrillary acidic protein (hGFAP) promoter to examine the effect of miRNAs in the developing *** found that ablation of miRNAs resulted in a smaller cerebellum,mis-positioned Purkinje neurons,decreased proliferation and increased apoptosis in granule neuron precursors,decreased number of basket and stellate intemeurons and aberrant morphology of Bergmann *** addition,Notchl signaling appears to be blocked in miRNA-ablated Bergmann *** further identified miR-9 as differentially expressed in Bergmann glial cells,and its expression was promoted by Notchl *** also demonstrated that cortical radial glia exhibited normal morphology in the absence of miRNAs and yet reduced radial glial marker expression at embryonic stage,and that the postnatal radial glial transition to astrocytes was promoted in miRNA-ablated *** results further stressed the critical involvement of miRNAs in the developing CNS including cerebellum and provided first evidence of differential miRNA function in regulating radial glial phenotype in different regions of the developing CNS.

关键词： hGFAP miR-9 Dicer Cre-flox Bergmann glia

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Therapeutical effect of Triptolide on AD transgenic mouse model

Therapeutical effect of Triptolide on AD transgenic mouse mo...

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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： Bing XIAO,Qi WANG,Yan ZHENG,Xiao-Min WANG~* Department of Physiology,Key Laboratory of the Neurodegenerative Disorders of the Chinese Ministry of Education Capital Medical University,No.10 Xitoutiao Street,Youanmen,Beijing 100069,China

Objective Alzheimer's disease(AD) is a progressive neurodegenerative disorder that affects the elderly. The etiology of AD is still ***,a converging line of evidence indicates that brain inflammation induced by P-amyloid(Aβ) deposition is closely associated with the pathogenesis of this ***(named as T10) is an extract from the traditional Chinese herb Tripterygium Wilfordii Hook F(TWHF).It has been identified as the major component responsible for the immunosuppressive and anti-inflammatory effects of *** previous study has elucidated that it provides neuroprotection for AD in *** present study is to explore whether it has the therapeutical effect on AD in *** 5XFAD transgenic mice model and its wild type control were intraperitoneally injected with T10 and NS,*** water maze and immunohistochemistry assaying were performed to detect behavioral and histopathological changes in these mice mentioned ***(1) Behavior of 5XFAD transgenic mice treated with T10 has been improved in Morris water maze test.(2) Immunohistochemistry data indicated that T10 reduced the aggregation of Aβ.Conclusion Triptolide(T10) has some therapeutical effects on AD.

关键词： Alzheimer's disease Triptolide 5XFAD transgenic mice

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The production of Ap in APP stably transfected HEK293 cells was reduced by overexpression of Tyro 3

The production of Ap in APP stably transfected HEK293 cells ...

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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： Qi WANG,Yan ZHENG,Xiao-Min WANG~* Department of Physiology,Key Laboratory of the Neurodegenerative Disorders of the Chinese Ministry of Education Capital Medical University,No.10 Xitoutiao Street,Youanmen,Beijing 100069,China

Objective Tyro 3 is one of receptor tyrosine kinases in the TAM(Tyro 3,AXL and Mer) family,which is preferentially expressed in the neocortex and CA1,CA3 of hippocampus,and mainly associated with neurons. However,the relationship between tyro 3 and B-Amyloid(AB) is *** study is to investigate the relationship between Tyro 3 and AB *** We transfected APP plasmid to HEK293 cells and then selected by G418 to get HEK293 cells stably expressing APR CMV-Tyro 3-CFP and CMV-GFP reporter plasmids were used to transfect the cells mentioned above,***,the cells were treated with Gas6,which is the native ligand of Tyro *** supernatant AB was detected by *** We observed that the production of AB was decreased in HEK293 cells transfected with CMV-Tyro 3-CFP compared with that of CMV-GFP transfected ***,the effect was reversed by treatment of Gas6 to the *** In summary,our studies demonstrate that overexpression of Tyro 3 has the potential to reduce the generation of ***,the effect of Tyro 3 on the production of AB is independent of Gas6.

关键词： Tyro 3 receptor Gas6 HEK293 Aβ

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Neuroanatomical characteristics of "acupoints" in the rat determined by CTB-Alexa488,594

Neuroanatomical characteristics of "acupoints" in the rat de...

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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： Jing-Jing CUI,Wan-Zhu BAI~* Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences,Beijing 100700,China

Objective Neural tracing technique,as an advanced neuroanatomical approach,has been applied for the morphological study on the acupuncture for 30 *** aim of this study is to investigate the correlation between acupoint and nervous system using a new generation of fluorescent neural tracer,cholera toxin subunit B conjugated with Alexa Fluor 488,594(CTB-Alexa488,594).It will help us to further understand the neuroanatomical characteristic of *** Micro-injection with CTB-Alexa488 or CTB-Alexa 594 was carried out in the acupoints of "Chengshan","Jinggu"and "Dazhong" in the adult male SD *** 3 surviving days,the rat's brain,spinal cord and dorsal root ganglia(DRGs)were dissected following perfusion with 4%paraformaldehyde, cut into sections and observed under fluorescent microscope equipped with a digital *** neurons labeled by CTB-Alexa 488 and CTB-Alexa 594 were recorded and *** Under the fluorescent microscope system,the labeled neurons with CTB-Alexa 488 and CTB-Alexa 594 appeared in green and red respectively,and located ipsilaterally on the injection *** sensory and motor neurons innervating each acupoint distributed on the corresponding DRGs and spinal *** The present fluorescent tracing technique may be quite useful for investigating the neuroanatomical basis associated with different acupoints.

关键词： innervation cholera toxin subunit B conjugated with Alexa Fluor 488/594(CTB-Alexa 488/594) sensory neuron motor neuron

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Carbonic anhydrase I:a new player in ALS pathology

Carbonic anhydrase I:a new player in ALS pathology

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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： Armin AKAHAVAN Robert BOWSER Department of Cancer Biology California Pacific Medical Center Research InstituteSan FranciscoCA 94103USA Department of Pathology University of Pittsburgh School of Medicine200 Lothrop St.PittsburghPA 15261USA

Objective Carbonic anhydrase I(CA I) protein levels were found to be significantly increased in the spinal cords of both mutant SOD1-linked and sporadic ALS *** I is the cytoplamic isoform of the CA family which comprises of a total of 16 *** is not known how change of CA I might be related to ALS *** aims of this study are:(1) determine whether CA I is expressed in motor neurons in the spinal cord;(2) determine how is this expression is affected by ALS at the cellular level;(3) explore the mechanism by which CA I might play in ALS *** Immunohistochemistry and fluorescent immunostainning techniques were used to determine the pattern and changes of CA I expression in human spinal *** biochemistry and Western Blot analysis were used to examine the potential mechanism of subcellular location of CA ***(1) CA I is expressed in the motor neurons in human spinal cord;(2) a subpopulation of CA I is associated with ER membranes;(3) CA I change in ALS is more enhanced with membrane-associated CA *** CA I might play a role in ALS pathology via ER stress-mediated pathway.

关键词： carbonic anhydrase I motor neurons ALS ER stress

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Endocannabinoid signaling modulates synaptic transmission in the rat inner retina

Endocannabinoid signaling modulates synaptic transmission in...

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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-Han WANG~#,Yi WU~#,Yan-Ying MIAO,Xiao-Fang YANG,Zhong-Feng WANG~* Institutes of Brain Science,Institute of Neurobiology and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

Cannabinoid signaling system plays an important role in regulation of many neuronal functions in the CNS. Endocannabinoids function as a retrograde signaling to regulate the synaptic plasticity via activating presynaptic CB1 receptors in many brain *** date,the effects of this signaling on synaptic transmission in retina are poorly *** the present study,we aimed to explore the modulation of cannabinoid signaling on glycinergic and GABAergic inhibitory inputs,and glutamatergic excitatory inputs to retinal ganglion cells(RGCs)by patch-clamp techniques in rat retinal *** results show that activation of presynaptic CB1 receptors in both GABAergic and glycinergic amacrine cells(ACs)suppressed the frequency of miniature inhibitory postsynaptic currents(mIPSCs)in the RGCs through inhibiting the presynaptic voltage-gated calcium *** the effect of cannabinoid on glutamatergic excitatory inputs from bipolar cells to the RGCs is basically similar,the tonic inhibitory inputs from the ACs to the bipolar cells are *** these inhibitory inputs eliminated completely the suppression effect of cannabinoid on the excitatory inputs to the *** underlying mechanism is that deinhibition-induced depolarization of bipolar cells inactivates the presynaptic T-type calcium channels that is a target of the activated presynaptic CB1 receptors in the bipolar *** data revealed a new mechanism of cannabinoid modulating synaptic transmission in the inner retina.

关键词： cannabinoid CBl receptor inner retina mlPSCs mEPSCs deinhibition

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The neurotoxicity mediated by astrocytes involved in fragile X syndrome

The neurotoxicity mediated by astrocytes involved in fragile...

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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： Qi YANG,Kun ZHANG,Bin FENG,Yan-Yan GUO,Zhao-Hui XU,Jie HAN,Lan MA,Yu-Mei WU, Ming-Gao ZHAO~* Department of Pharmacology,School of Pharmacy,Fourth Military Medical University,Xi'an 710032,China

Fragile X syndrome(FXS) is a common inherited mental retardation caused by the lack of fragile X mental retardation protein(FMRP) due to silencing of the FMR1 *** studies suggest glia play an important role in the progression of some neurodevelopmental disorders,which including *** we found that knockout astrocytes from a fragile X mouse cannot support the normal dendritic morphology in the coculture *** their conditioned medium,we confirmed Fmrl KO astrocytes caused the abnormal neuronal growth via the neurotoxic ***,we found that Neurotrophin-3(NT-3) and glutamate were both elevated released in KO astrocytic conditioned medium(ACM).Moreover,we identified that(1) excessive NT-3 was attributed to the oxidative stress in FXS,(2) increased glutamate synthesis and release was resulted from higher expression of glutaminase and vesicular glutamate transported(VGLUT2) in Fmrl KO astrocytes,(3) overeproduction of NT-3 and glutamate in WT ACM can mimic the abnormal neuronal morphology in KO *** results support that astrocytes contribute to the dysregulated neurodevelopment of FXS and astrocytic NT-3 or glutamate production could be a therapeutic target for FXS.

关键词： Fragile X syndrome astrocytes neurotrophin-3 glutamate neurotoxicity

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