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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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Activation of ATP-sensitive potassium channels antagonize nociceptive behavior and hyperexcitability of DRG neurons from rats

Activation of ATP-sensitive potassium channels antagonize no...

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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-Na DU,Chao WANG,Hai-Lin ZHANG~* The Key Laboratory of Neural and Vascular Biology,Ministry of Education,Department of Pharmacology,Hebei Medical University,Shijiazhuang,China

Nociceptive responses to noxious stimuli are initiated at peripheral nociceptor *** channels play a vital role in pain signal initiation and *** of K channels has been implicated in mediating the analgesic effects of agents such as ***,systematic studies regarding the effects of K activators on nociception and neuronal excitability are *** this study,we describe the antagonistic effects of K activators pinacidil and diazoxide on nocifensive behavior induced by bradykinin（BK）,thermo and mechanical stimuli,and the bradykinin-induced hyperexcitability of DRG *** also found that K activators can moderately activate K in DRG *** the effects of K activators can be reversed by the K blocker glyburide,direct activation of K is most likely the underlying *** systematic study clearly demonstrates that activation of K could have significant modulatory effects on the excitability of sensory neurons and thus on sensory behaviors,such as nociception.K activators can be evaluated clinically for the treatment of pain symptoms.

关键词： KATP potassium channels DRG excitability nociception pinacidil diazoxide glyburide

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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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Orientation-selective information encoded and decoded in human primary visual cortex

Orientation-selective information encoded and decoded in hum...

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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： Kang Cheng Support Unit for Functional Magnetic Resonance Imaging,and Laboratory for Cognitive Brain Mapping,RIKEN Brain Science Institute,2-1 Hirosawa,Wako,Saitama 351-0198,Japan

In this presentation,I will introduce the results from two of our recent high-resolution functional magnetic resonance imaging(fMRI) *** the first experiment,we used a newly developed continuous and differential mapping method to demonstrate that the responses of individual voxels are tuned to stimulus *** the second experiment,we used a Fisher's linear classifier to show that subject's perceived stimulus orientations can be reliably ***,we found that the voxels that best encode(as in the first experiment) and decode(as in the second experiment) orientation-selective information are those closely associated with large venous vessels that run on the cortical surface.I will discuss these findings in relation to the interpreted relationship between decoded information using fMRI data and its underlying neuronal mechanisms and stress the importance of studying the neurovascular relationship at the level of cortical columns and intracortical vasculature.

关键词： Orientation-selective information encoded and decoded in human primary visual cortex

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Characteristics of eye movements in major depression

Characteristics of eye movements in major depression

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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： Zhen-Lan JIN~(1,*),Zhong ZHENG~2,Miao ZHOU~1 1 School of Life Science and Technology,University of Electronic Science and Technology of China,No.4,Section 2, North Jianshe Road,Chengdu 610054,China 2 West China School of Medicine,Sichuan University,48 Xiao Xue Road,Chengdu 610041,China

Objective We have compared saccadic eye movements between major depressed and normal people to find out characteristics of eye movements in depressed *** Depressed and normal subjects watched positive,neutral,or negative pictures and they were required to press a button as soon as they found smiling faces. Results We found smaller saccades amplitudes and larger pupil in depressed subjects compared to normal subjects regardless of types of ***,fixation durations were longer in depressed subjects only when watching neutral pictures and more fixation numbers were found in depressed subjects when watching positive pictures. Importantly,average pupil size significantly correlates with the HAMD(Hamilton Depression Rating Scale) score that the HAMD score gets higher as average pupil size gets *** These results demonstrate that depressed people have special characteristics of eye movements compared to normal people and particular aspect of eye movements even has potential power of predicting stages of depression.

关键词： eye movements fixation saccades pupil size major depression

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Autophagic-lysosome pathway activation promotes ox-LDL degradation by HUVECs

Autophagic-lysosome pathway activation promotes ox-LDL degra...

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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 HAN~1,Yan-Lin ZHANG~(1,2),Shou-Jiang YOU~(1,2),Li-Fang HU~(1,2),Ya-Ping YANG~(1,2),Yong-Jun CAO~(1,2),Chun-Feng LIU~(1,2,*) 1 Institute of Neuroscience,Soochow University,suzhou 215000,China 2 Second Affiliated Hospital of Soochow University,Neurology,suzhou 215000,China

Objective Autophagy is a process which can be activated during various stress *** previous study reported that oxidized low-density lipoprotein(ox-LDL) can activate autophagy in human umbilical vein endothelial cells(HUVECs).This study was designed to determine whether HUVEC utilized the autophagic pathway to get rid of this extracellular *** The ox-LDL content in HUVECs at different time point was measured by flow *** colocalization of Dil-ox-LDL with autophagic proteins and the detection of autolysosome formation were identified by ***(1) Autophagy activation decreased ox-LDL content in HUVECs.(2) Ox-LDL trafficking through the autophagic pathway.(3) Induction of autophagy upregulates the fusion of *** The activation of autophagic-lysosome pathway may accelerate ox-LDL degradation in HUVECs.

关键词： autophagy ox-LDL degradation HUVECs lysosome

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Different properties of TH-positive neurons in the midbrain and prefrontal cortex

Different properties of TH-positive neurons in the midbrain ...

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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： Rui ZHENG,Yong-Hong WANG,You-Sheng SHU~* Institute of Neuroscience,State Key Laboratory of Neuroscience,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

In the midbrain,typical dopamine neurons are clustered in areas known as ventral tegmental area（VTA）, substantia nigra（SN）,and retrorubral field（RRF）,expressing tyrosine hydroxylase（TH,a rate-limiting enzyme in dopamine synthesis）.They play an important role in many high-level cognitive processes,as reward,addiction,and so ***,although TH positive（TH） cells have also been found in the cortex,their function is so far still *** we perform immunohistochemical and electrophysiological experiments on TH neurons in both midbrain and cortex of the mouse,and preliminary results show that they are distinct in terms of both distribution and electrophysiological *** with the TH neuron in the midbrain,those in the cortex distribute more sporadically,fire narrower action potentials,and have higher firing *** differences in properties might have important functional implications,and this particular subgroup of TH neurons in the cortex might participate in the dopamine system through an unconventional way.

关键词： dopamine system TH-positive neurons midbrain prefrontal cortex

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Intracellular mechanisms underlying α2A-adrenergic suppression of prefrontal cortical excitatory synaptic transmission in rats

Intracellular mechanisms underlying α2A-adrenergic suppress...

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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 YI~1,Fei LUO~1,Xue-Han ZHANG~1,Bao-Ming LI~(1,2,*) 1 Institute of Neurobiology & State Key Laboratory of Medical Neurobiology,Institutes of Brain Science,Fudan University,Shanghai 200032,China 2 Center for Neuropsychiatric Diseases,Institute of Life Science,Nanchang University,Nanchang 330031,China

Stimulation ofα-adrenoceptors（ARs） in the prefrontal cortex（PFC） produces a beneficial effect on cognitive functions such as working ***α-adrenergic agonist guanfacine has been used for treatment of psychiatric disorders such as attention-deficit/hyperactivity disorder（ADHD）.A previous study in our laboratory showed that stimulation ofα-AR suppresses excitatory synaptic transmission in pyramidal cells of the rat medial prefrontal cortex（mPFC）.However,the intracellular mechanism underlying theα-AR suppression remains unclear. In the present study,we recorded evoked excitatory postsynaptic current（eEPSC） in layerⅤ-Ⅵpyramidal cells of the mPFC,using whole-cell patch-clamp recording technique,and found that theα-AR inhibition of excitatory synaptic transmission is mediated via Gi-cAMP-PKA-PP1 and/or Gi-cAMP-PKA-PP1-CaMKII signaling pathways.

关键词： α2A-adrenoceptor excitatory synaptic transmission intracellular mechanism medial prefrontal cortex rat

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Biomarkers and drug targets of Alzheimer's disease

Biomarkers and drug targets of Alzheimer's disease

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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： Jian-Zhi WANG Pathophysiology Department,Key Laboratory of the Chinese Education Ministry for Neurological Disorders,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

Alzheimer's disease(AD) is the most common cause of dementia affecting 47%in the population at age over *** there are licensed treatments that can alleviate the symptoms of AD,the efficacious diseasemodifying treatments are still *** pathophysiological process of AD is believed to begin many years before the diagnosis of dementia and this long preclinical phase would provide opportunity for the *** for improving diagnosis are moving forward,but a better consensus is needed to elucidate the link between the pathological cascade of AD and the clinical *** on the prevailing scientific evidence to date,a panel of biological and neuroimaging biomarkers that support clinical diagnosis have been developed recently,but further work is needed to understand these better and to establish whether interventions can substantially lower these *** this seminar,we will provide an overview of recent evidence regarding the biomarkers or drug targets of *** these molecules are solely intended for research purposes and do not have any clinical implications at this time,we believe that these biomarkers can provide a common rubric to advance the preclinical studies of AD,and ultimately,aid the field in moving toward earlier intervention of AD when some disease-modifying therapies may be most efficacious.

关键词： Alzheimer Biomarkers and drug targets of Alzheimer's disease

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Adjudin attenuates lipopolysaccharide-induced neuroinflammation

Adjudin attenuates lipopolysaccharide-induced neuroinflammat...

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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： Jia-Xiang SHAO,Qian Reuben XIE,Ye-Wei LIU,Wei-Liang XIA~* Neuroscience and Neuroengineering Center,School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University,Shanghai 200030,China

Neuroinflammation caused by microglial activation plays a key role in brain *** are activated in response to diverse stimuli and release multiple inflammatory *** seek for new drugs to modulate neuroinflammation,we recently found that Adjudin,a potential non-hormonal male contraceptive,exhibits additional function to reduce production of proinflammatory mediators in lipopolysaccharide(LPS)-stimulated microglial *** our present study,one-hour Adjudin pretreatment reduced IL-6 and IL-ip mRNA levels in BV2 microglial ***-6 secretion was also reduced with Adjudin *** determine whether Adjudin might have similar effects in vivo,mice were given Adjudin(100 mg/kg,i.p.) 3 h before and post LPS injection(2.5 mg/kg,i.p.). The results showed that Adjudin decreased the induction of IL-6 and IL-1P mRNA by LPS in the ***,our data suggest that Adjudin might mitigate neuroinflammation.

关键词： Adjudin neuroinflammation IL-6 IL-1β BV2 microglial cells lipopolysaccharide

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