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VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch

VGLUT2-dependent glutamate release from nociceptors is requi...

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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： Yang LIU Omar Abdel SAMAD Ling ZHANG Bo DUAN Qing-Chun TONG Claudia LOPES Ru-Rong JI Bradford B LOWELL Qiu-Fu MA Dana-Farber Cancer Institute and Department of Neurobiology Harvard Medical School 1 Jimmy Fund Way Boston Massachusetts 02115 USA Pain Research Center Department of Anesthesiology Brigham and Women''s Hospital and Harvard Medical School Boston Massachusetts 02115 USA Division of Endocrinology Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School 99 Brookline Ave. Boston Massachusetts 02215 USA

Itch can be suppressed by painful stimuli, but the underlying neural basis is *** generated conditional null mice in which VGLUT2-dependent synaptic glutamate release from mainly Nav 1.8-expressing nociceptors was *** mice showed deficits in pain behaviors including mechanical pain, heat pain, capsaicin-evoked pain, inflammatory pain and neuropathic *** pain deficits were accompanied by greatly enhanced itching, as suggested by i) sensitization of both histamine-dependent and histamine-independent itch pathways, and ii) development of spontaneous scratching and skin ***, intradermal capsaicin injection promotes itch responses, as opposed to pain responses in control *** conditional Vglut2 mutant mice thereby emulate human chronic itch syndromes in which painful stimuli paradoxically promote *** studies suggest that synaptic glutamate release from a group of peripheral nociceptors is required to sense pain and suppress *** of VGLUT2 in these nociceptors creates a mouse model of chronic neurogenic itch.

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Apaf1 deletion rescues injury-induced neuronal death after optic nerve injury

Apaf1 deletion rescues injury-induced neuronal death after 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届会员代表大会

作者： Xin GAO Kevin K.Park Zhigang HE Bin CAI Rugen Therapeutics R&D (Shanghai) Co. Ltd 555 Dongchuan Road Shanghai 200241 China Key Laboratory of Brain Functional Genomics (Ministry of Education) Institute of Cognitive Neuroscience East China Normal University 3663 North Zhongshan Road Shanghai 200062 China F.M.Kirby Neurobiology Center Children''s Hospital and Department of Neurology Harvard Medical School 300 Longwood Avenue Boston MA 02115 USA Key Laboratory of Brain Functional Genomics (Ministry of Education) Institute of Cognitive Neuroscience East China Normal University 3663 North Zhongshan Road Shanghai 200062 China

In the adult mammals, axotomy of mature neurons in the central nervous system (CNS) triggers massive cell death and failure to spontaneous axon *** relationship between axotomy-induced neuronal death and axon regeneration has not yet well-understood, although promoting intrinsic capability of axon regeneration of CNS neurons is often accompanied by moderately improved neuronal *** we generated a mouse line with conditional knock-out of apoptotic protease activating factor 1 (Apfa1).Apaf1 was deleted in retina ganglion cells (RGCs) by intravitreal injection of AAV-Cre virus, followed by optic nerve *** data show that although Apaf1 is deleted, RGCs have significantly a high survival rate, but their axon regeneration ability is not ***, axon regeneration is not the consequence of rescuing neuronal death.

关键词： Apaf1 conditional knock-out apoptosis axon regeneration

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Comparative study in the spontaneous response of the medial geniculate body and inferior colliculus in rats with thalamic reticular nucleus lesion after contralateral cochlear ablation

Comparative study in the spontaneous response of the medial ...

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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： Dan-Yi LU Shi-Gang HE Ju-Fang HE Laboratory of Applied Neuroscience Department of Rehabilitation Sciences The Hong Kong Polytechnic University Hung Hom Kowloon Hong Kong China CAS-Hong Kong Joint Research Laboratory for Visuo-Auditory Integration Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China State Key Laboratory of Brain and Cognitive Sciences Institute of Biophysics Chinese Academy of Sciences 15 Datun Road Beijing 100101 China CAS-Hong Kong Joint Research Laboratory for Visuo-Auditory Integration Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China

Tinnitus is a ringing, swishing, or other type of noise that originated in the ear or *** hypothesize that damage of the cochlear hair cells causes hypersensitivity of the cells after a period of reorganization in the auditory pathway.A malfunctioning of the thalamic reticular nucleus (TRN) would decrease its inhibition to the auditory transmission and eventually causes *** the present study, we would investigate the neuronal property change in the medial geniculate body (MGB) and inferior colliculus (IC) of the rats after cochlear ablation and TRN lesion at different *** acid was injected into the TRN to lesion the *** contralateral cochlea to the recording hemisphere was ablated under an operating *** responses of the MGB and IC were recorded with the implanted extracellular electrodes while the rat was in different physiological *** found that neurons in the auditory thalamus should more changes than those in the *** results would lead us to a further investigation on the potential mechanism focusing on the changes in the MGB.

关键词： Tinnitus cochlea thalamic reticular nucleus (TRN) medial geniculate body (MGB) inferior colliculus (IC)

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Activation of KCNQ potassium channels by small chemical moleculars

Activation of KCNQ potassium channels by small chemical mole...

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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： Zhaobing GAO Min LI Department of Neuroscience High Throughput Biology Center and Johns Hopkins Ion Channel Center School of Medicine Johns Hopkins University Baltimore Maryland 21205 State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 555 Zu Chong Zhi Road Zhangjiang Hi-Tech Park Shanghai 201203 China State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 555 Zu Chong Zhi Road Zhangjiang Hi-Tech Park Shanghai 201203 China

KCNQ potassium channels play a critical role in controlling membrane *** a typical voltagegated ion channels (Kv), KCNQ channels undergo closed to open transitions by sensing transmembrane potential changes and mediate inhibitory potassium *** of KCNQ channel activity as results of genetic mutation is causal to a variety of human diseases including epilepsy, arrhythmia and ***, discovery of small compounds to activate voltage-gated ion channels is an important strategy for clinical intervention in human diseases caused by membrane hyperexcitability, including anxiety, epilepsy, arrhythmia and neuropathic *** the binding of these molecules induces a conformational change leading to the opening of these channels, there is also a considerable conceptual interest in understanding the molecular basis of these "gain of a function" *** molecule activators of cation channels are rare; however, several novel compounds have been identified for KCNQ potassium ***, we reported two new molecules which potentiate either cardical or neuronal KCNQ channels and identified molecular determinants for their activity, which provide exciting insights into activation of voltage-gated channels by small molecuars.

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Balanced dopamine is critical for pattern completion during associative memory recall

Balanced dopamine is critical for pattern completion during ...

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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： Fei LI L.Phillip WANG Xiaoming SHEN Joe Z.Tsien Brain and Behavior Discovery Institute Medical College of Georgia Augusta Georgia United States of America Brain and Behavior Discovery Institute Medical College of Georgia Augusta Georgia United States of America Department of Developmental and Behavioral Pediatrics of Shanghai Children''s Medical Center & Shanghai Key Laboratory of Children''s Environmental Health XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China Department of Developmental and Behavioral Pediatrics of Shanghai Children''s Medical Center & Shanghai Key Laboratory of Children''s Environmental Health XinHua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Objective Pattern completion, the ability to retrieve complete memories initiated by partial cues, is a critical feature of the *** study investigates the role of dopamine in memory *** We have analyzed dopamine transporter heterozygous knockout mice (DAT+/2).Results (1) While these mice possess normal learning, consolidation, and memory recall under full cue conditions, they exhibit specific deficits in pattern completion under partial cue condition; (2) This form of memory recall deficit in the dopamine transporter heterozygous knockout mice can be reversed by a low dose of the dopamine antagonist haloperidol, further confirming that the inability to retrieve memory patterns is a result of dopamine *** Our results reveal that a delicate control of the brain's dopamine level is critical for pattern completion during associative memory recall.

关键词： memory retrieval Dopamine pattern completion

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Phosphodiesterase-5 inhibitor Viagra,erectile dysfunction,and CNS diseases

Phosphodiesterase-5 inhibitor Viagra,erectile dysfunction,an...

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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： Heng-Ming KE The University of North Carolina at Chapel Hill,USA

Cyclic nucleotide phosphodiesterases(PDEs) hydrolyze the second messengers adenosine and guanosine 3',5'-cyclic monophosphates(cAMP and cGMP) to 5'-AMP and 5'-*** one of human PDE genes are categorized into 11 families and encode>100 isoforms of PDE proteins via alternative mRNA *** selective PDE inhibitors have been widely studied as therapeutics for treatment of human diseases,such as schizophrenia and *** most successful examples of this drug class is the PDE5 inhibitor sildenafil that has been marketed as Viagra for the treatment of male erectile dysfunction and Revatio for the treatment of pulmonary *** addition,PDE5 inhibitors have been studied for the treatment of various human diseases, including(1) lower urinary tract symptoms(LUTs),(2) benign prostatic hyperplasia,(3) cardiovascular disorders,(4) ischemia-reperfusion,(5) acute adrenergic contractile stimulation,(6) chronic hypertrophy,(7) dysfunction attributable to pressure-overload,and(8) chronic heart ***,PDE5 inhibitor Viagra has been shown to improve the spatial memory and to decrease Abeta levels in the APP/PS 1 mice,suggesting its potential for the treatment of Alzheimer's disease.

关键词： PDE Phosphodiesterase-5 inhibitor Viagra,erectile dysfunction,and CNS diseases CNS

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The role of macroautophagy and chaperon-mediated autophagy in huntingtin metabolism

The role of macroautophagy and chaperon-mediated autophagy 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： Zheng-Hong QIN,Fang LIN,Jun-Chao WU,Lin QIN Deartment of Pharmacology,Soochow University School of Medicin,Suzhou 215123,China

A neuropathological hallmark in human HD and mouse models is the intracellular accumulation and aggregation of N-terminal Htt fragments,suggesting that aberrant Htt proteolysis and/or dysfunction in clearance of truncated Htt may underlie the neuropathology of *** a cell model of HD overexpressing Htt fragment 1-552 amino acid residues(Htt-552).We found that both macroautophagy and chaperon-mediated autophagy(CMA) were involved in degradation of *** the levels of macroautopahgy and CMA effected the accumulation of *** can interact with Htt-552 and redistributed from nucleus to the cytosol and knockdown of beclinl increased the accumulation of mutant Htt552,suggesting macroautophagy regulator beclinl plays a role in promoting degradation of *** of cell lysates containing expressed Htt-552 with isolated lysosomes demonstrated that Htt-552 bound to lysosomes and was transported into the lysosomal lumen for *** of polyQ tract in Htt-552 impaired its uptake and degradation by *** of putative KFERQ motif in wilt-type Htt-552 interfered with interactions between Htt-552 and *** data suggest that CMA also plays a role in Htt *** studies indicate that both macroautophagy and CMA are involved in degradation of Htt and thus may represent an important therapeutic target.

关键词： The role of macroautophagy and chaperon-mediated autophagy in huntingtin metabolism

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The possible mechanism of Ca2+ induced Ca2+ release in astrocytes

The possible mechanism of Ca2+ induced Ca2+ release in astro...

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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： Jun-Hua YANG,Ke-Qing ZHU,Shu-Min DUAN~* Department of Neuroscience,School of Medicine Zhejiang University,Hangzhou 310058,China

Objective Astrocytes are the primary neuronal structural and trophic supportive *** like neurons which can generate action potential,however astrocytes exhibit diversity intracellur calcium activity and this is thought to play an important part in physiology and pathological *** calcium elevation has various forms,one important is Cainduced Ca release（CICR）which is thought to be mediated by 1,4,5-triphosphate receptor（IP3R）and ryanodine receptor（RyR）but the mechanism is not very *** our research,we want to explore the potential mechanism of CICR by a new *** We used laser scan confocol microscopy to monitor the intraculler calcium variation and used a special method triggering Cainflux in mouse *** inhibitors of different channels were use to investigate the possible role of participating in *** Astrocytes calcium elevation was significantly inhibited by some specificity *** Our primary datas showed that NCX may play an important role in astrocytes *** contrary to some papers which reported RyR relating to CICR,our study didn't find this result.

关键词： astrocytes 1,4,5-triphosphate receptor ryanodine receptor Na+/Ca2+ exchangers

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14-3-3 proteins interact with the neurofilament light subunit and regulate neurofilament dynamics

14-3-3 proteins interact with the neurofilament light subuni...

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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-Qing MIAO,Jun-Lin TENG~*,Jian-Guo CHEN~* Department of Cell Biology,College of Life Sciences,Peking University,Beijing 100871,China

Neurofilament light subunit(NFL) is the core component of neurofilaments,which are the main intermediate filaments(IF) in *** dominant inherited diseases are related to mutations in IF *** studies report that NFL mutations are related to the charcot-marie-tooth(CMT) diseases,but the mechanism is ***,we show that seven 14-3-3 isoforms all interact with NFL,which is dependent on the phosphorylation of NFL head domain that is regulated by *** mutation analyses reveal many Serine phosphorylation sites in the head domain that are important for 14-3-3 *** of these sites lead to aggregate ***,14- 3-3 overexpression increases NFL exchange rate and leads to neurofilament *** mutations P8Q,P8L, P22S,found in CMT diseases,inhibit 14-3-3 binding and result in the formation of NFL aggregations,which can be rescued by 14-3-3 ***,14-3-3 proteins regulate NFL assembly and dynamic exchange through interaction with NFL,and can act as potential molecule targets for therapy of human CMT diseases.

关键词： NFL 14-3-3 neurofilament phosphorylation CMT

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Lysosomal exocytosis in Schwann cells contributes to axon re-myelination

Lysosomal exocytosis in Schwann cells contributes to axon 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： Gang CHEN~1,Zhijun ZHANG~2,Qiong CHENG~1,Zhongya WEI~1,Xia LI~1,Shumin DUAN~3,Xiaosong GU~1 1 Jiangsu Key Laboratory of Neuroregeneration,Nantong University,Nantong,226001,Jiangsu,China 2 Med-X Research Institute of Shanghai Jiao Tong University,Shanghai 200031,China 3 Department of Neurobiology,Zhejiang University School of Medicine,Hangzhou 310058,China

Myelin biogenesis is a complex process involving coordinated exocytosis,endocytosis,mRNA transport and cytoskeletal *** abnormalities of myelin are common in lysosomal storage diseases,our understanding of the role of lysosomes in the formation and maintenance of myelin is still *** we show that lysosomes in Schwann cells contain abundant myelin protein PO,which accounts for over half the total protein of compact myelin in the peripheral nervous system,and exhibit Ca-dependent exocytosis in response to various *** regulation of Rab27a,a small GTPase required for the trafficking of the secretory lysosomes to the plasma membrane,largely blocked lysosomal exocytosis in Schwann cells and inhibited the re-myelination of regenerated sciatic *** findings highlight a novel role for lysosomes in Schwann cells and suggest that the regulated lysosome exocytosis in Schwann cells may have important physiological and pathological significance in the peripheral nervous system.

关键词： Lysosomal exocytosis in Schwann cells contributes to axon re-myelination

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