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Spatiotemporal Dynamics and Regulation of Multiple Contraction Centers in Migratory Neurons

Spatiotemporal Dynamics and Regulation of Multiple Contracti...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jian Jiang Zheng-hong Zhang Xiao-bin Yuan Mu-ming Poo Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain ScienceShanghai Institutes for Biological SciencesChinese Academy of Sciences Graduate School of the Chinese Academy of Sciences

Traction force against the substrate is required for neuronal migration, but how it is generated and regulated remains controversial. Using traction force microscopy, we showed in cultured granule cells the coexistence of three distinct contraction centers(CCs) that are located at the distal and proximal regions of the leading process as well as at the trailing process, regions exhibiting high-level myosin-II activities. The activities of CCs depended on myosin-II, actin filaments, and were regulated by microtubules and substrate adhesion, and exhibited apparently independent fluctuation. The difference of strain energies associated with CC activities between leading versus trailing processes tightly correlated with the displacement of the soma at any given time. Application of brain-derived neurotrophic factor(BDNF) and Slit2, factors known to guide neuronal migration, at the leading process altered CC activities by regulating the small GTPases Cdc42 and Rho A, respectively, leading to forward and rearward soma translocation. These results delineate the multiple origins and spatiotemporal dynamics of the traction force underlying neuronal migration.

关键词： contraction center,neuronal migration,traction force,myosin-II,BDNF

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药物基因组学分析提示PTPRD基因多态性与非典型抗精神病药致体重增加关联

药物基因组学分析提示PTPRD基因多态性与非典型抗精神病药致体重...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者：郁昊王力芳吕路线马翠翠杜波卢天兰金超阎浩杨勇锋李文强阮燕燕张鸿燕张红星宓为峰马文斌栗克清张岱岳伟华北京大学精神卫生研究所/第六医院卫生部精神卫生学重点实验室暨国家精神心理疾病临床医学研究中心(北京大学) 北京大学-清华大学生命科学联合中心新乡医学院第二附属医院重点实验室河南省精神病医院锦州市康宁医院河北医科大学精神卫生研究所北京大学IDG麦戈文脑科学研究所

目的:抗精神病药治疗期间出现体重增加直接影响患者对治疗的依从性,已成为精神疾病治疗中的严重问题,应给予足够的重视。本研究采用药物基因组学研究方法,寻找与非典型抗精神病药引起的体重增加相关的单核苷酸多态性位点。方法:选择完成... 详细信息

目的:抗精神病药治疗期间出现体重增加直接影响患者对治疗的依从性,已成为精神疾病治疗中的严重问题,应给予足够的重视。本研究采用药物基因组学研究方法,寻找与非典型抗精神病药引起的体重增加相关的单核苷酸多态性位点。方法:选择完成8周非典型抗精神病药治疗的534例精神分裂症患者,进行全基因组单核苷酸多态性位点检测。随后选择同样治疗方案的精神分裂症568例患者作为独立验证样本,采用Sequenom平台进行测序。并针对只服用利培酮和喹硫平的236例患者进行单独分析。最后,针对显著关联的多态性位点进行表达数量性状分析(expression quantitative trait locus,e QTL)。结果:蛋白酪氨酸磷酸酶D型受体(protein tyrosine phosphatase,receptor type D,PTPRD)上的2个SNP位点,谷氨酰胺果糖-6-磷酸转氨酶2(glutamine:fructose-6-phosphate amidotransferase 2,GFPT2)上的1个SNP位点与非典型抗精神病致体重增加显著相关,多重检验矫正后3个SNP位点达全基因组显著关联水平(P<5×10-8)。该结果在独立样本中及只服用利培酮与喹硫平的患者中得到验证。eQ TL分析结果显示显著关联位点会影响所在基因的表达。结论:蛋白酪氨酸磷酸酶D型受体单核苷酸多态性与抗精神病药治疗导致汉族精神分裂症患者体重增加显著相关。

关键词：精神分裂症体重增加非典型抗精神病药药物基因组学单核苷酸多态性蛋白酪氨酸磷酸酶D型受体

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母孕期慢性温和性应激对子代成年大鼠类焦虑、抑郁行为以及GABA-A受体表达的影响

母孕期慢性温和性应激对子代成年大鼠类焦虑、抑郁行为以及GABA-A...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者：麻钰超李晓白中国医科大学附属第一医院心理科

目的:本研究通过观察母孕期慢性温和性应激以及类焦虑或抑郁行为对子代成年大鼠杏仁核、前额叶皮质GABA-A受体表达的影响,来探讨焦虑或抑郁症的发病机制,为临床治疗提供理论依据。方法:采用随机分组原则将孕鼠分为对照组和应激(PS)组。... 详细信息

目的:本研究通过观察母孕期慢性温和性应激以及类焦虑或抑郁行为对子代成年大鼠杏仁核、前额叶皮质GABA-A受体表达的影响,来探讨焦虑或抑郁症的发病机制,为临床治疗提供理论依据。方法:采用随机分组原则将孕鼠分为对照组和应激(PS)组。在孕期最后两周对应激组施加慢性温和性应激。月龄为3月大的子代进行高架十字迷宫和强迫游泳实验,观察其行为学的变化。运用蛋白印迹技术检测大鼠杏仁核、前额叶皮质GABA-A受体表达量的变化。结果:PS组子代雌、雄大鼠进入开放臂的相对次数和时间百分比明显减少,不动时间明显延长,表明PS组雌、雄子代类焦虑行为和类抑郁行为增多。蛋白印迹结果显示PS组雄性大鼠杏仁核GABA-A受体α1(P<0.001)和β1(P<0.01)亚基的表达低于控制组;PS组雌性大鼠杏仁核GABA-A受体α1亚基表达低于控制组(P<0.01),GAD67的表达高于控制组(P<0.05)。高架十字迷宫导致子代大鼠杏仁核α1亚基和β1亚基高于非高架十字迷宫组(行为主效应显著:P<0.001),雌性-高架-控制组α1亚基低于雌性-高架-PS组(PS与行为交互效应显著:P<0.05)。在前额叶皮质,高架十字迷宫组α1亚基高于非高架十字迷宫组(行为主效应显著:P<0.001);雄性-高架-控制组α1亚基高于雌性-高架-控制组(性别主效应显著:P<0.05)。强迫游泳导致子代杏仁核和前额叶皮质脑区α1亚基高于非强迫游泳组(行为主效应显著:P<0.001);杏仁核脑区强迫游泳组β1亚基高于非强迫游泳组(行为主要效应显著:P<0.001),雄性-强迫游泳-控制组α1亚基高于雌性-强迫游泳-控制组(性别主效应显著:P<0.05)。结论:1、母孕期慢性温和性应激使子代类焦虑、抑郁行为增多。2、母孕期慢性温和性应激显著减少了大鼠杏仁核中GABA-A受体的表达。3、母孕期慢性温和性应激和行为都会影响子代杏仁核与前额叶皮质GABA-A受体的表达并且GABA-A受体的变化与高焦虑、抑郁表现相一致,提示GABA-A受体可能参与了孕期应激所致的精神疾病的病理生理过程。

关键词：母孕期慢性温和性应激焦虑抑郁杏仁核前额叶皮质 GABA-A受体

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Study of effect and mechanism of electroacupuncture on the abnormal discharge of motor cortical neurons in 6-OHDA Rat

Study of effect and mechanism of electroacupuncture on the a...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Min Sun Jun Hua Liu Jun Jia Xiaomin Wang Key Laboratory of Neurodegenerative Disease of the Ministry of Education Capital Medical University

Althoughpharmacological dopamine replacement therapy and deep brain electrical stimulation(DBS) can alleviate the motor symptoms of Parkinson disease(PD), side effects of drugs and a small fraction of patients with PD can take advantage of DBS. A significantly less invasive method—electroacupuncture(EA)—has been suggested as an alternative approach for symptomatic treatment of PD. However, the mechanisms underlying motor improvements through EA are unknown. In this study, unilateral injection of 6-hydroxydopamine(6-OHDA) was performed to set up a rat model of *** EA stimulation was used to analyze the effect on abnormal motor behaviors of PD rats. And at the same time, we detect the effect on motor cortex firing patterns after 4 weeks EA treatments to realize the intervention effect on motor cortex by EA stimulation. Here, we show EA gradually alleviates motor deficits in a rat model of PD. Neuronal recordings from motor cortex in parkinsonianrat revealed abnormalneural activityactivity in PD model. 100 Hz EA could downregulate beta oscillation, and also interfere with the Spike Triggered Average(STA) of beta oscillation, which was similar to the effect of L-dopa treatment, indicating that the motor cortex may be a potential taeget of EA stimulation.

关键词： Parkinson's disease,Electroacupuncture,Motor cortex,In vivo electrophysiology

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Inhibition of Nav1.8 channels reduces pain-related spontaneous activity in DRG after spinal cord injury

Inhibition of Nav1.8 channels reduces pain-related spontaneo...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Junhui Du Susan M.Carlton Neurosci & Cell Biol Univ.Texas Medical Branch

The severe, chronic pain that often follows spinal cord injury(SCI) is thought to depend upon alterations in spinal and supraspinal neurons. Our findings shows that an increased spontaneous activity(SA) in DRG is generated after contusion, and such increased SA lasts from 30 min to 2 months. It might contribute to central sensitization and neuropathic pain after SCI, just as nociceptor SA contributes to pain after peripheral injury and inflammation. Nav1.8 is a tetrodotoxin(TTX)-resistant voltage-gated sodium ion channel. It is expressed specifically in the dorsal root ganglion(DRG) small-diameter sensory neurons and is involved in the pain. The modulation of Nav1.8 in sensory neurons of the DRG may be the key factor in therapeutic targets for the development of new analgesics and to treat chronic pain. To test this hypothesis we are examining SA in possible nociceptors in vivo. A-803467, potently blocks NaV1.8 channels, was applied on the DRG. And the SCI induced SA was significantly block after A-803467 application. The results imply that Nav1.8 is an important target for exploring the mechanisms of SCI induced SA, and may provide a new area to treat chronic pain.

关键词： spinal cord injury,DRG,Nav1.8

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The Mechanical Effect of Surgical Trauma on Alcohol Administration

The Mechanical Effect of Surgical Trauma on Alcohol Administ...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jie Liu Xiaojian Li Hui Zhao Department of Integrative Medicine School of Basic Medical SciencesFudan University

Alcohol abuse and addiction are huge obsessions to people invoking severe social problem. Previous Studies show that trauma can enhance alcohol administration following neuroinflammation in TBI. Clinical surgical trauma can also cause neuroinflammation whose degree is constantly changing. Evidences uncovered that people post-surgery have greater preference to alcohol than common people producing enormous harm to patient and his family. So researching mechanism of surgical trauma to alcohol administration is urgent. In our work, we constructed surgical trauma model with male SD rats, then exposure to alcohol(10%, v/v) and water in 2-bottle choice drinking paradigm from post-trauma 1, 3, 7 day. And it conducted 4 hours and 24 hours each day for 19 days. Results indicate that 4-hour alcohol intake and preference show a significant increase in T3 compared with control and T1 in 24-hour testing. So surgical trauma can influence alcohol intake and preference in certain post-trauma stage, and the duration of taking alcohol can influence the response. In general, our research demonstrates the relationship between surgical trauma and alcohol administration and directs us to solve the problem of alcohol abuse and addiction.

关键词： Alcohol abuse and addiction neuroinflammation clinical surgical trauma

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The fine structure of the compound eye and optic lobe of the two-spotted cricket Gryllus bimaculatus

The fine structure of the compound eye and optic lobe of the...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jie Na Xue Leng Yu-Peng Na College of Chemistry & Life Sciences Shenyang Normal University Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications Ministry of Education of China

【Objectives】 To investigate the important structural pathway of insect visual signal processing by observing and describing the histological structural features of the compound eyes and optic lobes of the cricket, Orthoptera Gryllidae. 【Methods】The histological structure of the compound eye and optic lobe of 30 crickets was observed and analyzed using scanning electron microscopy and histological biopsy techniques. 【Results】 The compound eye was comprised of about 3,400 small hexagonal eyes. In the gaps between the small eyes, there are mechanoreceptors, which are sensory hair and bell-shaped receptors. Each small eye is comprised of a cornea, crystalline cone, rhabdome, 6 retinal cells and basement membrane, etc. The optic lobe has two fan-shaped structures and is comprised of three major networks of nerve fibers, the ganglion layer, outer medulla and inner medulla.【Conclusion】 There are a few sensory hairs and bell-shaped receptors on the surface of the compound eyes of crickets. Each small eye is comprised of a cornea, crystalline cone, rhabdome, 6 retinal cells, basement membrane, etc. and the arrangement of small eyes is juxtaposed. The optic lobe is comprised of three major networks of nerve fibers.

关键词： Gryllus bimaculatus,compound eyes,optic lobe,histological structure

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Histone demethylase PHF8 deficiency causes cognitive impairments through the mTOR pathway

Histone demethylase PHF8 deficiency causes cognitive impairm...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Weidong LI Shanghai Jiao Tong University

X-linked mental retardation(XLMR) is a heterogeneous condition affecting approximately 0.2% men, and there is currently no drug treatment. PHF8(plant homeodomain finger protein 8) is histone demethylase for H3K9me2 and H4K20me1, and mutations of the gene are found in X-link mental retardation patients. Here we show that PHF8 knockout impairs cognitive functions, including spatial learning and memory and contextual fear memory in mice, as well as the reduced long term potentiation in the hippocampus. m RNA profiling and chromatin immunoprecipitation indicate that PHF8 directly regulates RSK1, a ribosomal protein S6 kinase involved in the mT OR signaling. Using a pharmacological approach, we further demonstrate that a brief treatment with the mT OR inhibitor rapamycin can ameliorate the deficits of learning and memory, and reverse the long term potentiation in knockout mice. Thus, our results reveal that histone demethylase PHF8 deficiency causes cognitive impairment at least through the RSK-mT OR pathway, and targeting the mT OR pathway may have potential therapeutic effects on PHF8 associated X-link mental retardation.

关键词： PHF Histone demethylase PHF8 deficiency causes cognitive impairments through the mTOR pathway

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Acrylamide induces locomotor defects and degeneration of dopamine neurons in Caenorhabditis elegans

Acrylamide induces locomotor defects and degeneration of dop...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Jia Li Dan Li Yong-Sheng Yang Tian-Tian Xu Ping Li De-Fu He Lab of Toxicology School of Ecological and Environmental SciencesEast China Normal University Shanghai Key Lab for Urban Ecological Processes and Eco-Restoration

Acrylamide can form in foods during cooking process and cause multiple adverse effects. However, the neurotoxicity and mechanisms of acrylamide have not been fully elucidated. In Caenorhabditis elegans, we showed that 48 h exposure to 10-625 mg/L acrylamide resulted in significant declines in locomotor frequency of body bending, head thrashing, and pharynx pumping. In addition, acrylamide exposure reduced crawling speeds and changed angles of body bending. It indicates that acrylamide induce locomotor defects, along with Parkinsonian-like movement impairment including bradykinesia and hypokinesia. Acrylamide also affected chemotaxis plasticity and reduced learning ability. Using transgenic nematodes, we found that acrylamide induced down-expression of Pdat-1 and led to the degeneration of dopaminergic neurons. Moreover, the enhanced expression of unc-54, encoding a subunit of α-synuclein was found. It illustrates that acrylamide is efficient in inducing crucial Parkinsonian pathology including dopaminergic damage and α-synuclein aggregation. These findings suggest the acrylamide-induced locomotor defects and neurotoxicity are associated with Parkinson's disease.

关键词： Acrylamide Caenorhabditis elegans Locomotor behaviors dopaminergic neurons α-synuclein Parkinson's disease

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Genetic association and autoimmunological mechanisms of narcolepsy

Genetic association and autoimmunological mechanisms of narc...

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第六届亚太神经科学联合会学术会议暨中国神经科学学会第十一届全国学术会议

作者： Fang Han Department of Pulmonary Medicine Beijing University People's Hospital

Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and disturbed nocturnal sleep. Narcolepsy is caused by the loss of hypocretin(orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4(also called OX40L), Cathepsin H(CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. More recently, narcolepsy was identified in association with seasonal streptococcus, H1N1 infections in 2010 following the 2009 H1N1 pandemic(p H1N1) in China and following AS03-adjuvanted p H1N1 influenza vaccination in Northern Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons, and are likely a combination of genetic and environmental factors, such as upper airway infections.

关键词： Narcolepsy,H1N1,Gene,Hypocretin

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