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检索条件"任意字段=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"

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Physiological Basis of Brain Network Hubs Using BOLD and ASL fMRI

Physiological Basis of Brain Network Hubs Using BOLD and ASL...

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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：贺永北京师范大学

该研究首先采用血氧水平依赖脑功能成像技术(BOLD-f MRI)构建了静息态下人脑上万个节点(脑体素)的功能连接网络,并计算了每个节点的连接强度(FCS)来衡量其重要性。进一步,采用动脉自旋标记灌注脑功能成像技术(ASL-f MRI)测量了静息态下... 详细信息

该研究首先采用血氧水平依赖脑功能成像技术(BOLD-f MRI)构建了静息态下人脑上万个节点(脑体素)的功能连接网络,并计算了每个节点的连接强度(FCS)来衡量其重要性。进一步,采用动脉自旋标记灌注脑功能成像技术(ASL-f MRI)测量了静息态下的局部脑血流(rC BF)水平,并通过计算其与功能连接强度的空间相关来研究两者之间的关系。结果发现,大脑功能网络的中枢节点主要分布于默认网络(内侧额顶皮层)、脑岛和视觉皮层,并显示出和r CBF显著的空间相关性,特别是FCS和r CBF在默认和执行控制网络中表现出比视觉和感觉运动网络更高的空间相关性,并随着任务强度的增加而显著增强。研究结果阐释了人脑功能连接组的代谢和生理基础,并对进一步加深理解人脑认知加工的神经机制,揭示人脑正常发育、老化和神经精神疾病(如阿尔茨海默病、抑郁症)中脑功能连接组的变化,以及研究脑疾病早期诊断的影像标记物等临床问题具有重要潜在价值。

关键词： BOLD ASL fMRI 脑网络连接组学

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台湾遗传性运动感觉神经病变的分子基因遗传研究

台湾遗传性运动感觉神经病变的分子基因遗传研究

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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：李宜中台北荣民总医院神经内科阳明大学神经学科

遗传性运动感觉神经病变,又称做Charcot-Marie-Tooth disease(CMT),是最常见的遗传性周边神经病变,其临床症状包括渐进性肢体远程肌肉萎缩无力、脚掌形变、远程感觉丧失及肌腱反应下降。CMT可进一步可藉由遗传的型式、发病的年龄、以及... 详细信息

遗传性运动感觉神经病变,又称做Charcot-Marie-Tooth disease(CMT),是最常见的遗传性周边神经病变,其临床症状包括渐进性肢体远程肌肉萎缩无力、脚掌形变、远程感觉丧失及肌腱反应下降。CMT可进一步可藉由遗传的型式、发病的年龄、以及电生理和病理的特征来做初步的分类;在台湾最常见的是第一型CMT(CMT1),也就是在儿童期或之后发病的体显性遗传的脱髓鞘型神经病变;而第二型CMT(CMT2)是体显性或隐性遗传的轴索病变型CMT。目前已有超过70种的CMT致病基因被发现,但仍有约有10%的CMT1及60%的CMT2病人的致病突变不明。我们近年来在约300个台湾CMT家系中进行超过二十种已知致病基因突变的筛检。我们同时也运用全外显子定序(Whole exome sequencing)的技术发现证明GNB4为一新型显性中间型CMT(Dominant Intermediate CMT;DI-CMT)的致病基因,而TFG基因突变会导致典型的CMT2。GNB4基因是用来制造G-proteinβ4 subunit(Gβ4),其为细胞中G-protein讯息传导系统中的核心成员之一。我们发现了两个CMT病患家族分别带有GNB4 p.G53D及p.K89E突变。运用免疫荧光组织染色法,我们发现病人腓神经中的axons与Schwann cells内都含有丰富的Gβ4蛋白。我们同时也运用细胞模式证明突变的Gβ4 G53D与Gβ4 K89E会使Gβ4相关的G-protein讯息传导路径发生障碍。而由G蛋白晶体立体结构模型可推测此二GNB4基因突变发生在Gα与Gβ4的交界面上,因而可能会影响Gβ4与各种Gα的相互作用。我们的研究首度揭露了Gβ4相关的细胞讯息传导系统在周边神经系统功能运作上的重要性。TFG基因的突变首先是由日本学者在2012年8月所报导。他们在四个CMT的HMSN-P亚型(hereditary motor and sensory neuropathy with proximal dominant involvement)家系中发现p.P285L显性突变。HMSN-P的临床表现与典型CMT最大不同之处在于病患的肌肉萎缩无力的部位在肢体的近端,而非一般CMT以远程肌肉萎缩无力为主的特征。TFG蛋白被发现广泛存在于人类细胞中的内质网出口(endoplasmic reticulum exit sites),它会形成oligomer,它的功能是帮助在内质网内合成的蛋白质分泌出内质网。我们在一个庞大典型CMT2家系中发现了TFG p.G269V突变,功能性分析显示此突变会使在细胞内的TFG蛋白容易形成聚集而使能自由发挥作用的TFG分子数量减少。如果压抑细胞内TFG蛋白质的生成会减损细胞内蛋白质分泌功能;而这缺损可被增加正常型TFG蛋白表现来矫正,而无法以增加突变型TFG蛋白表现来矫正。此研究首度发现证明TFG的基因突变为典型CMT2之致病基因。

关键词：神经病变基因突变 CMT 基因遗传

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TFP5 prevents degeneration of DA neurons in a MPTP-induced PD mouse model

TFP5 prevents degeneration of DA neurons in a MPTP-induced P...

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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：张奇山姬仲谢惠芳贺荣霓何勇黄建欧许苗菁潘速跃胡亚芳南方医科大学南方医院神经内科

Parkinson's disease(PD) is a leading neurodegenerative disorder causing severe motor disabilities. Besides the hallmark pathology of the specific loss of dopaminergic(DA) neurons in the substantia nigra pars compacta(SNpc) and the formation of intracytoplasmic Lewy bodies that are mainly composed of fibrillar a-synuclein. CDK5/p35 activity is essential for early neurodevelopment in mammals. However, endogenous calpain dependent cleavage of p35 to p25 is associated with neuron death. It has been reported that hyperactivity of CDK5/p25 in PD brains is partly responsible for the PD pathology. Here, we indicated that p25 was increase by MPP + treated primary rat cortical neurons and caused cell apoptosis. TFP5, a modified truncated 24-aa peptide(TFP5) and specifically inhibited CDK5/p25 activity, significantly inhibited MPP+-induced cell apoptosis. In the SNpc area of MPTP-induced PD mice, p25 was markedly increased, whereas DA neuron showed by TH staining significantly lost(up to 30–40%). TFP5 successfully penetrated in BBB, rescued DA neuron loss, inhibited the hyperphosphorylation of MEF2D and alpha-synuclein, and prevented DA neurons against apoptosis. No rescue was observed in mice injected with either saline or scrambled peptide. While TFP5 had no effect on acute motor deficits, it improved behavior deficits in open field experiment for PD mice. These results suggest TFP5 as a potential therapeutic candidate for PD.

关键词： Parkinson's disease MPTP cyclin-dependent kinase 5 p35 p25 dopaminergic neurons TFP5

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A study of scratch-induced transforming growth factor (TGF) in astrocytes

A study of scratch-induced transforming growth factor (TGF) ...

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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： Hsi Cheng Liu Jiang Shan Zhan Kai Gao Xi Huajia Rui Chao Chai Yuan Jin Feng Jiang Jiaohuajiang Albert Cheung Hoi Yu Neuroscience Research Institute Peking University and Department of NeurobiologySchool of Basic Medical Sciences Key Laboratory for Neuroscience of the Ministry of Education and Key Laboratory for Neuroscience of the National Health and Family Planning Commission Peking University

Under the conditions of cerebral trauma and spinal cord injury, quiescent astrocytes are rapidly activated to release cytokines resulting in an inflammatory response. The balance between anti-inflammatory factors and proinflammatory factors is crucial to the inflammatory process. Recent findings in cellular biology suggest that inflammation may provide a potential explanation for the tumors progress. The transforming growth factor(TGFs) family plays an important part in inflammation and tumor metastasis. In our laboratory, we used an in vitro scratch model to induce inflammation. We compared astrocytes, the benign tumor cell line(DU145) and the malignant tumor cell line(A549, MCF7) in cell migration after scratch. We also detected the TGF-βm RNA level in astrocytes and cancer cells using qR T-PCR. In order to distinguish the endogenous response and exogenous influence after scratch injury, we set two experimental groups, which are the scratching & changing the media(S&C) group and the scratching without changing the media(S) group. We found that the levels of TGF-βm RNA were decreased in S group. We also observed that the levels of TGF-β m RNA level differed between the S&C group and the S group, indicating exogenous influence was important in the transcription of TGF-β. In conclusion, we found that the inflammation involved both endogenous response and exogenous influence after scratch injury.

关键词： inflammation TGF-β astrocyte scratch model

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结合光学影像及大脑皮层电描技术探讨周边刺激对急性期缺血性脑卒中的功能性恢复

结合光学影像及大脑皮层电描技术探讨周边刺激对急性期缺血性脑卒...

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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：冯先锋郭立威王照婷陈嘉伟张晴柔陈右颖赖欣怡浙江大学求是高等研究院系统神经与认知科学研究所国家卫生研究院生物医学工程和医药研究所国立阳明大学生物医学工程系

脑卒中已被确认为全球第三大死因,其中缺血性脑卒中占了约87%。脑卒中发作后,由于血管的阻塞,血液无法正常流通到其他脑组织从而缺血和坏死,导致永久性的神经损伤或死亡,受影响的大脑区域可能会失去相应功能。最近的研究表明,对于大脑... 详细信息

脑卒中已被确认为全球第三大死因,其中缺血性脑卒中占了约87%。脑卒中发作后,由于血管的阻塞,血液无法正常流通到其他脑组织从而缺血和坏死,导致永久性的神经损伤或死亡,受影响的大脑区域可能会失去相应功能。最近的研究表明,对于大脑中动脉闭塞的啮齿类动物模型,在脑卒中发作2小时内给予胡须刺激,可保护局部脑组织免于缺血和阻止预期的脑组织损害。然而在应用中确切的时间、计量和脑区相应关系仍然不是很清楚。因此,我们制作了啮齿类动物光化学诱导局部脑卒中的模型,并给于末梢区域刺激,使用激光散斑对比度成像(Laser Speckle Contrast Imaging,LSCI)和大脑皮层电描技术(electrocorticography,ECoG)观察脑卒中后皮质功能的变化,并试图优化刺激寻找治疗脑卒中的适当时机。本研究中,共使用45只右半球前肢躯体感觉皮质血栓形成局部脑卒中(S1FL)的雄性老鼠(Sprage dawely,300-350 g),均分成前肢刺激组,后肢刺激组和控制组,每组中再分成5只老鼠实行激光散斑对比度成像、5只老鼠实行大脑皮层电描技术量测、5只老鼠实行氯化三苯基四唑(2,3,5-triphenyltetrazolium chloride,TTC)染色切片。激光散斑对比度成像用于测量老鼠皮层脑血流量在脑卒中前后随时间的变化,大脑皮层电生理技术被用于测量神经细胞的活性,并进一步计算相干性(Coherence),从而了解脑卒中前后脑区间相干性变化。氯化三苯基四唑是一种氧化还原指标,由于脱氢酶的作用使得正常的区域和梗死区域颜色不同,由此可评估了老鼠大脑卒中面积。激光散斑对比度成像的结果表明,前肢刺激组的动物在脑卒中后,其相对血流量在大脑前动脉和大脑中动脉区域并没有随着时间的推移而减少。反之,后肢刺激组与控制组会因前肢躯体感觉皮质梗塞造成相对血流量大量减少。脑皮层电描技术的相干性分析在显示,前肢刺激组在90分钟后前肢躯体感觉皮质的相干性呈现一个上升趋势,而后肢刺激组与控制组的相干性在脑卒中后皆呈现下降的趋势。氯化三苯基四唑染色也显示了同样的趋势,后肢刺激组和对照组的梗塞体积与前肢刺激组相比明显较大。正如前面结果表明,电刺激在正确相应区域可以提高侧枝循环的灌注,有助于功能的恢复。前肢刺激组的初级躯体感觉皮层感觉区的双侧连接高于其他组,同时这组的被侵害体积要小很多。因此,我们推测末梢区域相对皮层电刺激区域的脑卒中治疗可能有助于恢复或维持神经与血管的耦合和神经连接。

关键词：大脑局部缺血周边神经刺激脑血流量激光散斑对比度成像电生理信号功能性恢复

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Behavior responses in APP/V717I transgenic mice with gender difference during AD pathology processing

Behavior responses in APP/V717I transgenic mice with gender ...

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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： Yan Tan Zhang Qi Feng Wang Kaiyu Yang Qian Hua School of Preclinical Medicine Beijing University of Chinese Medicine

Alzheimer disease（AD）, one of the most common forms of dementia, is an age-dependent progressive neurodegenerative disorder with clinical occurrence of gender difference that female are more likely susceptible than male subjects. To demonstrate whether this gender difference happens in AD animal model and provide an evidence for further study in its mechanism and treatment target, we developed this study by using APP/V717 I transgenic na?ve mice with both genders to assess their cognitive behaviors. Amyloid precursor protein（APP）, a type I transmembrane protein which is cleaved by α-, β- and γ-secretase to form extracellular amyloid peptides pathologically. Mutations in APP are associated with early-onset of familial AD（FAD）. APP/V717I（London mutation） was the first mutation found linked to FAD residing near γ-secretase cleavage site. In this study, cognitive behaviors are test in open field test, Morris Water Maze and step-down test at six-month old and 10-month old, respectively. In six-month old, female transgenic mice showed a subtle higher anxiety than wide-type controls in open field test of time spent in center area（0%）;while in ten-month old, APP/V717 I male mice exhibited significant more anxiety compared with wide-type controls（0%）, but not female, suggesting that in APP/V717 I transgenic mice AD processing generated a relatively early effect on female anxiety but interestingly a more severely pathological progress on male anxiety. In Morris Water Maze, although there was no significant cognitive impairment occurred in both genders at six-month old, but female transgenic mice again showed a subtle impairment on spatial learning in term of latency to platform compared with wide-type controls;again interestingly, at ten-month old,male transgenic mice exhibited significantly worse spatial learning（latency to platform） than wide-type controls. This result of a more severely progressive cognition impairment in male is consistent with the result in open field te

关键词： Alzheimer disease behavioral test gender difference transgenic mice

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Neural mechanisms of self-motion perception perturbed by object-motion

Neural mechanisms of self-motion perception perturbed by obj...

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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： Xue-Fei Yu Han Hou Yong Gu Institute of Neuroscience and Key Laboratory of Primate Neurobiology Shanghai Institutes for Biological SciencesChinese Academy of Sciences University of Chinese Academy of Sciences

Accurate heading estimation could be derived from the radial patterns of the surrounding objects projected on the retina due to self-motion in the environment, which is so called "optic flow"(Gibson 1950). However, this process is typically complicated by presence of simultaneously moving objects independent on ego-motion, which could distort the optic flow field and thus bias heading judgments. Indeed, previous psychophysical studies have shown that introducing an independent moving object could bias the human's estimation of heading based on optic flow signals(Warren and Saunders, 1995;Royden and Hildreth, 1996). Yet, the underlying neural mechanisms still remained unknown. In the current study, we first established an animal model, showing that macaques' behavior in heading judgments was very similar to that observed on human beings. We then put electrodes into the monkeys' brain to record and manipulate neuronal activity in area MSTd and MT in the dorsal visual pathway. Our neurophysiological experiments showed that area MSTd was responsible for self-motion perception because neurons in this area contains large receptive fields and were best tuned to global visual motion field. Under the presence of independent moving object, the tuning of MSTd neurons was shifted such that a decoder's heading judgments based on these neurons were also shifted. We further proved that this biased signal was from area MT based on two facts. One was that in contrast to area MST, MT neurons contained small receptive fields, and were best tuned to local visual motion field. More importantly, microstimulation experiments showed that artificially activating MT neurons with small receptive fields during self-motion task significantly biased the animals' heading estimation, with the bias direction predictable from the tuning of the stimulated neurons. Finally, we constructed a two-layer back-propagation network in which MSTd pools neural activity from MT neurons. We showed that this mode

关键词： self-motion object-motion optic flow microstimulation macaque

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Physiological peripheral amyloid-beta clearance and its therapeutic potential for Alzheimer's disease

Physiological peripheral amyloid-beta clearance and its ther...

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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： Yang Xiang Xian-Le Bu Yu-Hui Liu Chi Zhu Lin-Lin Shen Shu-Sheng Jiao Xiao-Yan Zhu Brian Giunta Jun Tan Weihong Song Hua-Dong Zhou Xin-Fu Zhou Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical University Department of Laboratory Medicine Southwest HospitalThird Military Medical University Neuroimmunology Laboratory Department of Psychiatry and Behavioral NeurosciencesMorsani College of MedicineUniversity of South Florida Rashid Laboratory for Developmental Neurobiology Silver Child Development CenterDepartment of Psychiatry and Behavioral NeurosciencesMorsani College of MedicineUniversity of South Florida Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouverBritish Columbia School of Pharmacy and Medical Sciences and Sansom Institute University of South Australia

Amyloid-beta(Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease(AD). The physiological capacity of peripheral tissues and organs in clearing Aβ in the brain and its therapeutic potential for AD remains largely unknown. Here, we measured serum Aβ levels in different locations of the circulation in humans and mice, and used a parabiosis model to investigate the efficacy of peripheral Aβ catabolism on AD pathogenesis. We found that serum Aβ levels in the inferior/posterior vena cava were lower than that in the superior vena cava in both humans and mice. Additionally injected 125 I labelled Aβ40 was located mostly in the liver and kidney but very little in the brain, suggesting that Aβ derived from the brain can be cleared in the periphery. Parabiosis before/after Aβ deposition in the brain significantly reduced brain Aβ burden without alterations in the expression of amyloid precursor protein(APP), Aβ generating and degrading enzymes, Aβ transport receptors and attenuated AD-type pathologies such as tau phosphorylation, neuroinflammation, neuronal degeneration and loss in the brain of parabiotic AD mice. Our study revealed that the peripheral system is potent in clearing brain Aβ and preventing AD pathogenesis, suggesting that peripheral Aβ clearance is a valid therapeutic approach for AD.

关键词： Alzheimer's disease Amyloid-beta Peripheral clearance Pathogenesis

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Neuronal representations in the dorsolateral prefrontal cortex and the medial temporal lobe during a temporal-order-memory task

Neuronal representations in the dorsolateral prefrontal cort...

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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： Yuji Naya Cen Yang He Chen Wendy A Suzuki Department of Psychology and Beijing Key Laboratory of Behavior and Mental Health Peking University Center for life sciences Peking University IDG/McGovern Institute for Brain Research Peking University Center for neural science New York University

Episodic memory, the ability to remember our autobiographical events, contains temporal context in which the events took place. Neuropsychological studies have shown that the memory for the temporal-order of events or items is impaired in patients with lesions of either medial temporal lobe(MTL)(Mayes et al., 2001) or frontal lobe(Shimamura, 1990). In the present study, we recorded single-unit activities from both MTL and dl-PFC of non-human primates during a temporal-order memory task that requires the subjects to encode two visual objects and their temporal order(Naya and Suzuki, 2011), and compared the activity between the two brain regions directly. We found two types of task related neurons that may be involved in encoding the sequence of two objects in both regions. One group of neurons showed stimulus-selective responses for either the first cue or the second cue stimulus and are referred to as item cells. We found that dl-PFC, particularly its ventral part contained substantial number of item cells. However, their representation manner for integrating an item and its presented temporal order was different from those in MTL. Onset of stimulus-selective responses in dl-PFC was significantly later than the perirhinal cortex of MTL and visual area TE, but not the entorhinal cortex. In addition, only dl-PFC but not MTL carried item information of the first cue presentation until the next cue presentation. Another group of neurons showed different amplitudes of responses between two cue presentations and are referred to as order-selective neurons. We found that the dorsal part of dl-PFC provided an incremental timing signal representing the passage of time between the two cue presentations similar to hippocampus. These results indicate dl-PFC and MTL may work in the service of temporal order memory in a complementary manner.

关键词： time cell declarative memory

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Inhalation of rose essential oil decreased depression-like behavior in Wistar Kyoto rats

Inhalation of rose essential oil decreased depression-like b...

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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： Keng-Hoe Lok Sheng-Tian Li Bio-X Institutes Shanghai Jiao Tong University

Objective Depression is one of the most common psychiatric disorders that results in significant consequences in many countries. Clinicians managing depressed patients face two challenges: First, some antidepressants' therapies are associated with a variety of side effects. Second, longer time is needed for some antidepressants to work effectively. Such consequences cause medication non-adherence and discontinuation. In traditional manuscripts there are many indications about the anxiolytic effects of rose oil, and toxicity rarely occurs with appropriate use of essential oils. So far, however, less scientific research has been done about antidepressant effect of essential oil, even though this is one of the most commonly used aromatherapy. The purpose of present study was to determine the effects on depression like behaviors and underlying mechanisms of inhaled rose essential oil. Methods All experiments were carried out on 6 weeks old male WistarKyoto(WKY) rats. Rats were allowed to inhale rose essential oil's-, or its principal constituent β-Citronellol oil's vapors for 2 weeks(7 hours/day) in a special cage prior to performing the behavioral tests. Control animals were caged in the same conditions but in the absence of the tested oils. Locomotor activity of animals was measured by total distance travelled in open field test(OFT). The antidepressant activities of rose oil and β-Citronellol were assessed using the forced swim test(FST). Proteomic analysis using an isobaric tag for relative and absolute quantitation(iT RAQ) and tandem mass spectrometry was performed to identify differentially expressed proteins in the hippocampus of different groups. Then, some of the depression-related proteins were followed-up simultaneously in qR T-PCR, western blot, and immunohistochemistry assays. Results No significant alterations of locomotor activity in OFT were detected in oil-inhaled WKY rats. While significantly reduced immobile time(I.T) in FST were observed in WKY rats

关键词： Depression rose β-Citronellol

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