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不同频率的电针对环磷酰胺小鼠免疫功能的影响

不同频率的电针对环磷酰胺小鼠免疫功能的影响

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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：胡志苹黄志华黄诚赣南医学院生理教研室

目的研究不同频率穴位电针刺激对免疫功能低下小鼠免疫功能的影响。方法昆明小鼠随机分成5组,分别为:对照组、环磷酰胺（cyclophosphamide,CP）组、CP+2 Hz电针刺激（electroacupuncture stimulation,EAS）组、CP+100 HzEAS组、CP+2/100... 详细信息

目的研究不同频率穴位电针刺激对免疫功能低下小鼠免疫功能的影响。方法昆明小鼠随机分成5组,分别为:对照组、环磷酰胺（cyclophosphamide,CP）组、CP+2 Hz电针刺激（electroacupuncture stimulation,EAS）组、CP+100 HzEAS组、CP+2/100Hz EAS组,通过观察小鼠脾脏指数、NK细胞杀伤活性、脾细胞的增殖能力及外周血IL-6含量的改变,探讨不同频率EAS对环磷酰胺小鼠免疫功能的影响。结果（1）各频率单次电针刺激后0 h均可翻转环磷酰胺所诱导的NK细胞杀伤活性降低,其中以2/100 Hz交替频率的效果更好,24 h及48 h后无明显影响;（2）2 Hz及100Hz频率单次刺激后0 h抑制环磷酰胺所诱导的脾细胞增殖能力升高,2/100 HzEAS组的抑制效果不明显;24 h后,2 Hz及100 Hz EAS组继续显示抑制效应,而2/100 Hz EAS组使脾细胞增殖能力升高;48 h后各频率EAS组对脾细胞增殖无明显影响;（3）100 Hz及2/100 Hz交替频率连续3 d EAS组与CP组相比NK细胞杀伤活性、脾脏指数增高,脾细胞的增殖能力下降,2 Hz频率连续3 d电针组无明显变化;（4）连续3 d电针各组血清IL-6水平升高。结论各频率单次或连续穴位电针刺激对免疫功能低下小鼠的脾脏指数、NK细胞的杀伤活性、脾细胞的增殖能力及血清IL-6水平均有一定的影响;其中以2/100 Hz交替频率的穴位电针刺激效果更稳定,这些效应可能与电针刺激后升高IL-6的含量有关。

关键词：电针频率免疫功能

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白质消融性白质脑病患儿临床特点、基因突变分析及发病机制研究

白质消融性白质脑病患儿临床特点、基因突变分析及发病机制研究

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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：代丽芳吴晔冷雪荣王静敏潘艳霞杜丽朱赛楠姜玉武北京大学第一医院儿科北京大学第一医院医学统计室

目的对中国临床诊断为白质消融性白质脑病(VWM)的患儿进行真核细胞翻译启动因子2Bα-ε(eIF2Bα-ε)的相应编码基因EIF2B1-5突变分析,对17例确诊患儿进行自然病程的随访研究,以期对中国VWM患儿神经系统功能的进展速度等临床表型特点和... 详细信息

目的对中国临床诊断为白质消融性白质脑病(VWM)的患儿进行真核细胞翻译启动因子2Bα-ε(eIF2Bα-ε)的相应编码基因EIF2B1-5突变分析,对17例确诊患儿进行自然病程的随访研究,以期对中国VWM患儿神经系统功能的进展速度等临床表型特点和突变谱有全面的了解,并探讨基因型-表型关系。该病突出特点为发热等应激状态导致病情明显加重甚至死亡,由此研究内质网(ER)应激在VWM发病中的作用。方法 (1)对临床及基因突变检测诊断的17例早期儿童型VWM患儿,进行临床随访。根据运动进展速度进行分级,进行基因型-表型分析;(2)利用VWM患者皮肤成纤维细胞,给予ER应激诱导,于诱导后不同时相用Western blot和免疫细胞化学方法检测非折叠蛋白(UPR)通路的分子指标,并用电子显微镜观察细胞凋亡和自噬,Illumina RNA表达谱芯片进行差异基因检测和初步生物信息学分析,并与对照皮肤成纤维细胞进行比较。结果 (1)临床特点:17例中男12例,女5例。多数(13/17)起病前发育正常。起病年龄平均2.7岁(0.4～6.4岁),急性起病或亚急性起病,均以运动障碍起病。至末次随访,平均病程4.3年(0.3～8.7年),均呈进行性加重,3例死亡。64%(11/17)病程中伴发作性加重。运动功能进展速度明显高于国外报道病例,病程4.5年后所有患儿均丧失行走能力,最早丧失行走能力的年龄为起病后0.42年,起病年龄越小,丧失行走能力的年龄越早;认知功能进展缓慢;6例(35%)伴有惊厥。(2)基因突变分析:共发现了EIF2B2-5的22种突变,其中包括15种新突变。EIF2B3突变率显著高于国外报道,我们还发现了一个eIF2Bγ(EIF2B3编码)的热点突变p.I346T,35%中国患者带有该突变。(3)基因型-表型关系:重型患者中eIF2Bα突变者多于eIF2Bε突变者;相同基因型(eIF2Bγ:1346T)患者表型存在明显差异。(4)ER应激:①37℃培养条件下,基础状态下,UPR通路相关蛋白eIF2α磷酸化和ATF4水平在2例突变为eIF2Bγ:I346T/I346T和G47E/I346T患者皮肤成纤维细胞中表达量较正常人对照组明显增高。给予TG刺激后,突变细胞中eIF2α磷酸化和ATF4水平在TG刺激2h时升高最明显,且高水平表达持续至刺激8 h,较对照组表达量更大,更持久。对照组细胞eIF2α磷酸化和ATF4水平在TG刺激4 h时升高最明显,8 h时明显降低。基础状态下,P-eIF2Bε在突变细胞和对照组细胞中均有表达,且突变细胞较对照组表达量高,纯合突变细胞较杂合突变细胞中水平高。随着TG刺激时间的延长其活性条带在突变细胞中较对照组表达量升高明显。②35℃培养条件下,未给予TG刺激时,携带Bγ:G47E/I346T、Bγ:I346T/I346T突变的细胞与正常对照组中eIF2α磷酸化、ATF4及P-eIF2Bε水平均较37℃培养条件下高。给予细胞TG刺激,携带突变的细胞中eIF2α磷酸化和ATF4水平随着刺激时间的变化趋势与37℃时未见明显差异。③电镜显示Bγ:G47E/I346T突变患者皮肤成纤维细胞在基础状态下即存在大量自噬小体,ER应激诱导后8 h,细胞发生凋亡,且自噬小体进一步增加。④利用Illumina RNA表达谱芯片发现ER应激前后Bγ:G47E/I346T突变患者与正常人对照组皮肤成纤维细胞比较有34种差异表达的通路蛋白基因,结果需进一步验证。结论通过随访研究对中国早期儿童型VWM患者的主要神经系统表型的进展过程有了较详尽的了解。目前尚缺乏明确的基因型-表型相关性。中国患者基因突变谱与国外报道存在很大差异。内质网应激导致凋亡和自噬的发生可能在VWM的发病机制中扮演重要角色,低温对抵抗VWM突变细胞内质网应激的作用不明显。

关键词：白质消融性白质脑病磷酸化 ATF 皮肤成纤维细胞基因型-表型基因突变分析发病机制临床特点

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TRPC6 was neuroprotective in cerebral ischemia

TRPC6 was neuroprotective in cerebral ischemia

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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： Junbo HUANG,Xinxin HAN,Hailan YAO,Yizheng WANG Laboratory of Neural Signal Transduction,Institute of Neuroscience,Shanghai Institutes for Biological Sciences,State Key Laboratory of Neuroscience,The Graduate School,Chinese Academy of Sciences,Shanghai 200031,China

Neurons are the most vulnerable cells upon ischemic *** of neuronal survival is thus important for prevention of ischemic brain *** report that the transient receptor potential canonical(TRPC) 6 was neuroprotective in focal cerebral ***6 protein level in the neurons was greatly reduced in *** downregulation was specific for TRPC6 in the members of TRPC subfamily and mediated by calpain proteolysis.A peptide that contains a sequence spanning calpain cleavage site on TRPC6 protein specifically blocked TRPC6 ***,this peptide was neuroprotective against ischemic insults in both cultured neurons and *** level of phosphorylated cAMP-response element binding protein(pCREB) was maintained by the peptide,suggesting that the CREB signaling pathway was involved in the neuroprotective *** results indicated that suppression of calpain-mediated TRPC6 degradation preserved neuronal survival and prevented ischemic brain damage.

关键词： TRPC6 ischemia calpain neuroprotection

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The effect of aggregated α-synuclein on microglial activation

The effect of aggregated α-synuclein on microglial activati...

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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： Sen QIAO,Yi LI,Jian-Hong LUO,Jing-Hua JIN~* Department of Neurobiology,Zhejiang University School of Medicine,Hangzhou 310058,China

Objective A growing body of evidence indicates that neuroinflammation characterized by microglial activation probably contributes to the pathogenesis of Parkinson's disease(PD),and the mechanisms underlying microglial activation in PD are largely *** study is to explore whether aggregated a-synuclein can activate microglia and the mechanism underlying *** The activation of microglia was measured by morphological changes,neurotoxic factor production,and phagocytotic activity in BV2 cells as well as primary cultured rat microglia treated with aggregated *** Aggregated a-synuclein clearly changed microglial morphology and enhanced microglial production of extracellular NO,mRNA levels of IL-lβ,IL-6,COX-2,iNOS and phagocytotic *** Aggregated a-synuclein can induce microglial activation,and the underlying mechanisms are under study.

关键词： Parkinson's disease microglia aggregatedα-synuclein

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Two pairs of neurons in CNS control Drosophila innate light preference

Two pairs of neurons in CNS control Drosophila innate light ...

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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： Zhefeng GONG~*,Jiangqu LIU,Chao GUO,Yanqiong ZHOU,Li LIU~* State Key Lab.of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,15 Datun Road, Chaoyang District,Beijing 100101,China

Phototaxis is a basic response to environmental stimuli in the fruit fly Drosophila *** larvae,which prefer darkness to light,receive visual input from 2 bilateral groups of 12 photoreceptor neurons,known as the Bolwig's Organ(BO),which deliver output directly to pdf-expressing neurons in the central *** both the BO and pdf neurons causes blindness in larvae,suggesting that these neurons underlie the visual information flow that guides larval *** examined the neurons involved in larval phototactic behavior,and found that inhibiting the function of 2 pairs of larval CNS neurons that are putatively post-synaptic to pdf neurons results in a preference for light,as opposed to the preference for darkness observed in wild type *** results extend knowledge of the neural circuit that mediates larval phototactic behavior,and also elucidate the neural circuit that controls larval preference between light and darkness.

关键词： phototaxis behavior Drosophila larva

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Epigenetic regulation in Parkinson disease etiology

Epigenetic regulation in Parkinson disease etiology

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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： Cheng-Yuan TANG,Jie-Qiong TAN,Dan-Ling WANG,Zhuo-Hua ZHANG State Key Laboratory of Medical Genetics,Xiangya Medical School,Central South University,Changsha,China

It is well documented that both genetic and environmental factors play important roles in etiology of Parkinson disease(PD).Genetic studies of familial cases identify mutations in more than 10 genes causing *** pathophysiological function of these genes remains largely ***,a number of pesticides and herbicides induce parkinsonism in both human and animal *** of them are shown to regulate PD associated genes. During the past decade,we have interested in roles of genes-environmental factors interaction in PD *** results suggest that PD-related environmental factors contribute to PD etiology likely via epigenetically regulation of PD associated *** this presentation,we will discuss in detail PD associated epigenetic modification.

关键词： Epigenetic regulation in Parkinson disease etiology

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Pharmacological study of the light/dark preference test in zebrafish larvae

Pharmacological study of the light/dark preference test in z...

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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-Jiao CHEN,Gang PENG~* Institutes of Brain Science and State Key Laboratory of Medical Neuroscience,Fudan University,Shanghai 200032, China

Objective The zebrafish(Danio rerio) is emerging as a useful behavioral model of human anxiety. Here we further ascertain zebrafish larvae models of anxiety and validate the pharmacological effects of neuroactive compounds by the light/dark preference *** We provide a detailed description of the pattern of exploratory behaviours encountered in zebrafish larvae when exposed to the light/dark preference *** find that the larvae spend less time in the dark compartment relative to the white compartment of the testing *** expression of these dark-avoidance behaviours was significantly attenuated by anxiolytic(diazepam,lorazepam) drugs. Results The findings ascertain the nature of dark-avoidance behaviours as anxiety-like behaviours and provide the pharmacological validation of the light/dark preference test for zebrafish *** behavioural based assay can accommodate drug screening of neuroactive compounds.

关键词： zebrafish larvae anxiolytic drugs anxiety pharmacology

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A genetic labeling study of forebrain neuron development

A genetic labeling study of forebrain neuron development

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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： Chang-Wen ZHANG,He-Fei ZHANG,Liu Sun,Jing-Xia GAO,Gang PENG~* Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032, China

In the zebrafish forebrain,early developed dorsal telencephalic neurons extend their axons ventrally into the anterior commissure(AC)and the supraoptic tract(SOT).Previously it was unknown whether axons of these dorsal telencephalic neurons choose specific projection paths at the junction between the AC and the *** genetic labeling,we characterized the axon projection patterns of the dorsal telencephalon neurons at single cell *** results also revealed a weak correlation between the neuron soma position in the dorsal telencephalon and the axon projection *** are currently investigating the underlying intrinsic mechanisms of the projection choicesby microscopic and molecular genetics approaches.

关键词： zebrafish telencephalon AC SOT circuit formation

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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次会员代表大会

作者： Kevin K.Park F.M.Kirby Neurobiology Center Children's Hospitaland Department of NeurologyHarvard Medical School300 Longwood AvenueBostonMA 02115USA

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(Apfal).Apafl was deleted in retina ganglion cells (RGCs) by intravitreal injection of AAV-Cre virus,followed by optic nerve *** data show that although Apafl 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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Involvement of visuospatial sketchpad in abacus mental calculation:an ERP and fMRI case study

Involvement of visuospatial sketchpad in abacus mental calcu...

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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： Hong-Yuan LI,Yong-Di ZHOU,Yi-Xuan KU Institute of Cognitive Neuroscience,School of Psychology and Cognitive Science,East China Normal University, Shanghai,China

A large body of behavioral studies suggests that abacus mental calculation may use visuospatial strategy. However,there are still few functional imaging *** investigated an abacus expert with both visual and auditory addition *** ERP results showed that abacus mental calculation involve more parietal-occipital areas,compared with our former results in normal people,that is,the increase of the task difficulty engage more phonological loop in Baddeley's working memory *** fMRI activated brain areas include bilateral superior parietal cortices and bilateral supplemental motor *** combined results suggest the involvement of visuospatial sketchpad in abacus mental calculation.

关键词： Involvement of visuospatial sketchpad in abacus mental calculation:an ERP and fMRI case study ERP

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