记得几年前,我在接受新浪网的专访时,曾就包皮环切的问题做了一期访谈。其中对包皮的功能做了简单的介绍(访谈内容详见 http://www.dxyer.cn/andrologist/article/i30527.htm )。近来又有不少患者在门诊向我咨询这个话题,看来大家对于包皮的关注度还是很高的,因此觉得有必要对这个问题专门列个题目详细谈谈,于是就有了下面这篇博文: 包皮是上帝赠给灵长类,尤其人类最特殊而且珍贵的礼物,此礼物据信已在灵长类身体上保留了一亿年以上,既没有退化也没有进化。足见其功能与结构的确历经了千锤百炼,却始终屹立不摇。然而,在某些种族或宗教的文化里,为了顺应他们的社会传承或宗教仪式,在孩提时期或在行成人礼时,却将这个珍贵的礼物切掉作为祭品了。这个上帝的礼物就是包皮!当代,大多数医师尽管承认包皮是经过千万年进化史而被完整保留下来的东西,属于阴茎上的正常结构,但却仍认为包皮容易藏污纳菌、滋生感染,而且分泌的包皮垢易助长子宫颈癌的发生,所以他们多数建议尽早割除包皮。 果真像上面所讲的,包皮一无是处吗?或者因为只能当作某种仪式的图腾,而在功能簿上不能占有一席之地吗?又或者说它仅仅是人类进化史中尚未来得及彻底消亡的无用结构吗? 其实不然!因为到目前为止,它仍不是人体可有可无的痕迹器官(一为阑尾,一为第三臼齿),足见它必然具有一定的功能,只是我们以前把它给忽略了。因此,我想有必要为包皮作一些医学上的平反昭雪才对。 以下我们列举包皮的17项功能,并依其重要性按次序进行排列。 A:性生活 一、 增加性愉悦。系带处的感觉特别敏锐。 二、 在性交或自慰时,包皮内外板皮肤处于滑动状态,有着令人舒服的滚动感(rolling bearing)。 三、 因包皮内外板自身有滑动,减轻了对阴道壁的摩擦力,可避免性交疼痛。 四、 富裕的包皮可刺激伴侣生殖器,获得畅快。 五、 勃起时,提供因阴茎伸长所需的皮肤,避免束缚感。 六、 包皮可以储存费洛蒙(pheromone),且在性唤起时释出,充分调动伴侣的情欲。 七、 包皮可储存自然的润滑液(射精前液),在性兴奋时释出,性生活时起到润滑作用。 八、 性唤起时使龟头成为视觉刺激焦点。 九、 为精液提供一个暂时的容器,以减少在阴道壁上的耗损。 B:保护 十、 保护龟头,避免龟头皮肤过度角质化,保持松软湿润。 十一、保护薄皮的龟头(thin-skinned glans),使其免于受伤。 十二、保护龟头的神经,避免勃起功能受损。 十三、在孩童时,保护尿道口,免于污染或尿道感染。 十四、包皮分泌物中本来就有抗菌的成分,其中比较明确的就有溶菌酶,可发挥杀灭抑制病菌的作用。 十五、保护无色素的龟头,以免晒伤。 十六、保护血流供应本就不足的龟头,以免冻伤。(还记得Sir Ranulph Fiennes跨越北极区时龟头被冻伤的事情吗?) C:其它 十七、提供皮肤,供重建矫形手术使用。(如尿道下裂,眼睑烧伤) 由上述可知,包皮在人类是一种特殊的性感组织(erogenous tissue),如果千古名言饮食男女,人之大欲存焉?是对的话,那保留包皮势必有如羽化而登仙的效果。因此,在性功能研究逐渐成为热门学科之时,我们是否也应该还给包皮一个应有的地位,不要动不动就找理由把包皮给割了! 何况男性接受割包皮后,也常常丧失了珍贵的系带及其它功能,且疤痕处也可能形成神经瘤(Neuroma)。所以,除非万不得已,拙见认为应把包皮环切术的手术指证设定的更严格点,只有在内科治疗无效时,才可考虑。而当要行包皮环切术时,也须带着包皮美容的观念,尽量保留球状感觉接受体,Dartos肌肉、包皮粘膜等,并尽量避免龟头暴露,以免局部皮肤过度角化。 在众多的医学观点里,如澳州小儿外科学会、加拿大小儿医学会及小儿泌尿教科书中,都认为新生儿的龟头及包皮粘膜是一个复杂的融合体,还未发育成熟,更应谨慎是否行包皮环切术;在青少年期,最好也能清楚的告知男孩本人,最好等他们能明白割包皮的利弊得失后才可施行。碰到一些影响到小孩健康的包皮疾病,非开不行时,也须尽量保存包皮的结构及功能。如果医疗质量够高,所有切割下来的包皮都应该送病理检查,确定包皮环切术的适应症是不是抓对了! 当然不只医师要了解包皮的角色及功能,孩子的父母或成年患者本人也须提升对包皮的认知,唯有双管齐下,才能让无辜的包皮遭遇明镜本非台,何事惹尘埃之叹! 【附】包皮环切前后阴茎疲软和勃起状态比较 In order to appreciate the sexual functions of the foreskin, refer to Figures 15, which clarify what the foreskin is and how it works. Figures1 and2 show the difference between a circumcised and an uncircumcised penis in the relaxed or flaccid state. Note that the foreskin serves to cover the glans or head of the penis. Figure3 shows this diagrammatically. Figure 4 shows the circumcised penis in the erect state. The shaft skin is taut. Figure5 shows the uncircumcised penis before, during, and after erection. Note that the inner foreskin layer becomes exposed and the entire foreskin moves to loosely cover the penile shaft. Fig.1 包皮环切后处于疲软状态的的阴茎(Circumcised Penis in the Relaxed State) Fig.2 尚未环切的处于疲软状态的阴茎(Uncircumcised Penis in the Relaxed State) Fig3 包皮内板和外板的关系(Inner and Outer Foreskin Layers) Fig.4 环切后处于勃起状态的阴茎(Erectile Process in the Circumcised Penis) Fig.5 未环切阴茎的勃起过程(Erectile Process in the Uncircumcised Penis)
Endnote自从x2版本实现了可以直接找到全文的功能,很受大家欢迎,但也很多人反馈为什么很多全文明明有权限看却不能够找到全文? Endnote 找全文可以通过以下途径实现 : ISI web of knowledge和全文数据库做的链接(ISI上面的数据是文摘, 全文 字样是因为和全文数据库做了链接,可以直接通过链接到全文数据库下载全文) endnote web服务 DOI Pubmed的linkout链接 open url 因此最大化endnote找全文功能请: 关注是否有使用权限的全文数据库都和ISI做了链接 注册endnote web可以增加找全文的可能性 关注DOI号是否在DOI这个字段下,如果不在想办法归位 不要关闭IE的cookie保存 ps. 以前都在鸿波网开设博客,最近鸿波上不去了,转战到此,希望有老朋友惠顾!
http://www.sciencenet.cn/htmlnews/2009/9/223241.shtm 神经细胞内质网功能机理揭晓 50年谜题得解 瑞士弗雷德里希米歇尔生物医学研究所9月7日发布新闻公告称,该所科学家经过多年潜心研究,终于确定神经管微观网络内质网(ER)调节神经细胞间连接强度的功能机理。这一发现解答了困扰科学家长达50年的谜题,使人类对大脑学习和记忆的认识更深入了一步。相关研究成果发表在美国《国家科学院院刊》( PNAS )网络版上。 突触可塑性,即神经细胞间连接强度可调节的特性,对学习和记忆至关重要。神经细胞上的所有突触是否都具有相同的表达长期可塑性的能力,目前并不是很清楚。突触组织会影响局部信号级联的功能,进而对单个突触的可塑性进行差异性调控。这导致了大脑中神经细胞间突触连接的两种类型:一种连接会不断地形成、增强或减弱;另一些连接会则保持稳定状态,而正是这种状态使我们能够保持某种记忆很多年。 但突触组织的功能机理是怎样的?学界对此认识一直模糊不清。 瑞士弗雷德里希米歇尔生物医学研究所的神经生物学家托马斯奥特内尔带领一小组对CA1锥形神经细胞树突棘中的内质网是如何影响突触后信号的机理进行了研究,终于阐明了这种神经管微观网络的作用:正是神经细胞树突棘中内质网的存在决定了突触连接的稳定与否。这也是自1959年爱德华乔治格雷首次描述神经管微观网络内质网以来,科学家第一次阐明该结构的功能机理。 研究表明,在神经细胞树突棘中,内质网会有目标地选择含有强壮突触的大棘。当神经细胞受到刺激时,含有内质网的棘会释放大量的钙,从而引发突触功能的变化。对这些树突棘的低频刺激,会导致突触效力被长期抑制。相反,在缺乏内质网的棘中就没有这种功能的改变。因此,在同一个神经细胞中,两种类型的突触连接能够并存,并被单独控制。 公告称,奥特内尔的研究小组将下一步目标转到脆性X染色体综合征的研究上。作为最常见的一种遗传性认知障碍,该种病症患者会出现智力下降、学习困难、注意力不集中等问题。奥特内尔指出,该病症患者的神经树突棘会出现异常。他们怀疑,是含内质网的树突棘应激产生的信号级联在患者体内遭到过度刺激,才导致某些症状的出现。 http://www.pnas.org/content/106/35/15055.abstract?sid=da377557-7ade-4062-86a8-1985fc2cfa52 Differential distribution of endoplasmic reticulum controls metabotropic signaling and plasticity at hippocampal synapses Niklaus Holbro , sa Grunditz and Thomas G. Oertner , 1 + Author Affiliations Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland Edited by Roger A. Nicoll, University of California, San Francisco, CA, and approved July 22, 2009 (received for review May 8, 2009) Abstract Synaptic plasticity is considered essential for learning and storage of new memories. Whether all synapses on a given neuron have the same ability to express long-term plasticity is not well understood. Synaptic microanatomy could affect the function of local signaling cascades and thus differentially regulate the potential for plasticity at individual synapses. Here, we investigate how the presence of endoplasmic reticulum (ER) in dendritic spines of CA1 pyramidal neurons affects postsynaptic signaling. We show that the ER is targeted selectively to large spines containing strong synapses. In ER-containing spines, we frequently observed synaptically triggered calcium release events of very large amplitudes. Low-frequency stimulation of these spines induced a permanent depression of synaptic potency that was independent of NMDA receptor activation and specific to the stimulated synapses. In contrast, no functional changes were induced in the majority of spines lacking ER. Both calcium release events and long-term depression depended on the activation of metabotropic glutamate receptors and inositol trisphosphate receptors. In summary, spine microanatomy is a reliable indicator for the presence of specific signaling cascades that govern plasticity on a micrometer scale. long-term depression metabotropic glutamate receptor metaplasticity spine apparatus dendritic spines Footnotes 1 To whom correspondence should be addressed. E-mail: thomas.oertner@fmi.ch Author contributions: N.H. and T.G.O. designed research; N.H. and .G. performed research; N.H. analyzed data; and N.H. and T.G.O. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at 信息分析平台: http://www.gopubmed.org/web/gopubmed/1?WEB0b6tqs2ai913gIgI1I00d000j10040001rl 检索策略:Endoplasmic Reticulum and Nerve Cells and Synapses and Calcium and CA1 相关文献计量分析结果: Top Countries Publications USA 4 Switzerland 1 France 1 Belgium 1 Russia 1 Germany 1 Czech Republic 1 Italy 1 Top Cities Publications Basel 1 Boston 1 North Chicago 1 Gif-sur-Yvette 1 Lawrence 1 Mons 1 Moscow 1 Bethesda 1 Homburg 1 Hradec Krlov 1 Milan 1 Top Journals Publications J Neurosci 2 Proc Natl Acad Sci U S A 1 Nature 1 Pflug Arch Eur J Phy 1 Mol Brain Res 1 J Biol Chem 1 Biofizika+ 1 Neuroscience 1 J Physiol-london 1 Eur J Neurosci 1 1 2 3 ... 13 Top Terms Publications Endoplasmic Reticulum 11 endoplasmic reticulum 11 Synapses 10 Neurons 10 Hippocampus 10 Animals 10 Calcium 9 Dendrites 6 dendrite 6 Rats 6 pyramidal neuron development 5 pyramidal neuron differentiation 5 pyramidal neuron migration 5 intracellular 5 Pyramidal Cells 5 Plastics 4 Ryanodine Receptor Calcium Release Channel 4 ryanodine-sensitive calcium-release channel activity 4 Thapsigargin 4 Ryanodine 4 1 2 3 ... 13 1 2 3 Top Authors Publications Shen J 1 Zhang C 1 Wu B 1 Beglopoulos V 1 Wines-Samuelson M 1 Zhang D 1 Dragatsis I 1 Sdhof T 1 Stutzmann G 1 Chakroborty S 1 Goussakov I 1 Miller M 1 Chameau P 1 Van de Vrede Y 1 Fossier P 1 Baux G 1 Jols M 1 Wang J 1 Kelly P 1 Mackinnon R 1 1 2 3 相关研究报道: Title: Differential distribution of endoplasmic reticulum controls metabotropic signaling and plasticity at hippocampal synapses . PMID: 19706463 Related Articles Authors: Holbro, N , Grunditz, A , Oertner, T G Journal: Proc Natl Acad Sci U S A , 2009 Abstract: Synaptic plasticity is considered essential for learning and storage of new memories. Whether all synapses on a given neuron have the same ability to express long-term plasticity is not well understood. Synaptic microanatomy could affect the function of local signaling cascades and thus differentially regulate the potential for plasticity at individual synapses . Here, we investigate how the presence of endoplasmic reticulum ( ER ) in dendritic spines of CA1 pyramidal neurons affects postsynaptic signaling. We show that the ER is targeted selectively to large spines containing strong synapses . In ER-containing spines, we frequently observed synaptically triggered calcium release events of very large amplitudes. Low-frequency stimulation of these spines induced a permanent depression of synaptic potency that was independent of NMDA receptor activation and specific to the stimulated synapses . In contrast, no functional changes were induced in the majority of spines lacking ER. Both calcium release events and long-term depression depended on the activation of metabotropic glutamate receptors and inositol trisphosphate receptors. In summary, spine microanatomy is a reliable indicator for the presence of specific signaling cascades that govern plasticity on a micrometer scale. Affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel , Switzerland . Wikipedia: Calcium , Calcium metabolism , Dendrite , Dendritic spine , Depression , Endoplasmic Reticulum , Ergastoplasm , Glutamate receptor , Government , Inositol , Inositol metabolism , Metabotropic glutamate receptor , N-methyl-D-aspartate , N-methylaspartate , NMDA , Nerve cell , Neuron , Plastic , Receptors, glutamate , Receptors, metabotropic glutamate , Receptors, n-methyl-d-aspartate , Synapse Title: Presenilins are essential for regulating neurotransmitter release. PMID: 19641596 Related Articles Authors: Zhang, C , Wu, B , Beglopoulos, V , Wines-Samuelson, M , Zhang, D , Dragatsis, I , Sdhof, T C , Shen, J Journal: Nature , Vol. 460 (7255): 632-6 , 2009 Abstract: Mutations in the presenilin genes are the main cause of familial Alzheimer's disease. Loss of presenilin activity and/or accumulation of amyloid-beta peptides have been proposed to mediate the pathogenesis of Alzheimer's disease by impairing synaptic function. However, the precise site and nature of the synaptic dysfunction remain unknown. Here we use a genetic approach to inactivate presenilins conditionally in either presynaptic (CA3) or postsynaptic ( CA1 ) neurons of the hippocampal Schaeffer-collateral pathway. We show that long-term potentiation induced by theta-burst stimulation is decreased after presynaptic but not postsynaptic deletion of presenilins. Moreover, we found that presynaptic but not postsynaptic inactivation of presenilins alters short-term plasticity and synaptic facilitation. The probability of evoked glutamate release, measured with the open-channel NMDA ( N-methyl-D-aspartate ) receptor antagonist MK-801, is reduced by presynaptic inactivation of presenilins. Notably, depletion of endoplasmic reticulum Ca(2+) stores by thapsigargin, or blockade of Ca(2+) release from these stores by ryanodine receptor inhibitors, mimics and occludes the effects of presynaptic presenilin inactivation. Collectively, these results indicate a selective role for presenilins in the activity-dependent regulation of neurotransmitter release and long-term potentiation induction by modulation of intracellular Ca(2+) release in presynaptic terminals, and further suggest that presynaptic dysfunction might be an early pathogenic event leading to dementia and neurodegeneration in Alzheimer's disease. Affiliation: Center for Neurologic Diseases, Brigham Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston , Massachusetts 02115, USA . Pubmed MeSH: Animals , Calcium , Cells, Cultured , Gene Expression Regulation , Glutamic Acid , Hippocampus , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic Wikipedia: Alzheimer's Disease , Alzheimer disease , Axon terminal , Cistron , Dementia , Endoplasmic Reticulum , Ergastoplasm , Frontotemporal lobar degeneration , Gene , Genetic material , Long-term potentiation , Long term potentiation , Mutation , N-methyl-D-aspartate , N-methylaspartate , NMDA , Nature , Nerve cell , Neurohormones , Neuromodulator , Neuron , Neurotransmitter , Neurotransmitter agents , Pathogenicity , Peptides , Plastic , Polypeptides , Presenile dementia , Presenilin , Presynaptic terminal , Probabilities , Probability , Receptors, n-methyl-d-aspartate , RyR1 , RyR2 , RyR3 , Ryanodine , Ryanodine receptor , Ryanodine receptor calcium release channel , Semantic Dementia , Senile Dementia , Synaptic bouton , Synaptic terminal , Thapsigargin , Virulence Title: Deviant ryanodine receptor -mediated calcium release resets synaptic homeostasis in presymptomatic 3xTg-AD mice. PMID: 19641109 Related Articles Authors: Chakroborty, S , Goussakov, I , Miller, M B , Stutzmann, G E Journal: J Neurosci , Vol. 29 (30): 9458-70 , 2009 Abstract: Presenilin mutations result in exaggerated endoplasmic reticulum ( ER ) calcium release in cellular and animal models of Alzheimer's disease (AD). In this study, we examined whether dysregulated ER calcium release in young 3xTg-AD neurons alters synaptic transmission and plasticity mechanisms before the onset of histopathology and cognitive deficits. Using electrophysiological recordings and two-photon calcium imaging in young (6-8 weeks old) 3xTg-AD and non-transgenic (NonTg) hippocampal slices, we show a marked increase in ryanodine receptor ( RyR )-evoked calcium release within synapse-dense regions of CA1 pyramidal neurons . In addition, we uncovered a deviant contribution of presynaptic and postsynaptic ryanodine receptor -sensitive calcium stores to synaptic transmission and plasticity in 3xTg-AD mice that is not present in NonTg mice. As a possible underlying mechanism, the RyR2 isoform was found to be selectively increased more than fivefold in the hippocampus of 3xTg-AD mice relative to the NonTg controls. These novel findings demonstrate that 3xTg-AD CA1 neurons at presymptomatic ages operate under an aberrant, yet seemingly functional, calcium signaling and synaptic transmission system long before AD histopathology onset. These early signaling alterations may underlie the later synaptic breakdown and cognitive deficits characteristic of later stage AD. Affiliation: Department of Neuroscience, Rosalind Franklin University, The Chicago Medical School, North Chicago , Illinois 60064, USA . Pubmed MeSH: Disease Models, Animal , Humans , Mice, Transgenic , Neuronal Plasticity , Pyramidal Cells , RNA, Messenger , Receptor, Adenosine A1 , Synapses Wikipedia: Alzheimer's Disease , Alzheimer disease , Ammon's horn , Animal , Animal model , Animalia , Autoregulation , Calcium , Calcium metabolism , Cornu ammonis , Endoplasmic Reticulum , Ergastoplasm , Hippocampal formation , Hippocampus , Homeostasis , House Mouse , House mice , Isoforms , Laboratory mice , Laboratory mouse , Mice , Models, animal , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Mutation , Nerve cell , Neuron , Plastic , Presenile dementia , Presenilin , Protein isoforms , RyR1 , RyR2 , RyR3 , Ryanodine , Ryanodine receptor , Ryanodine receptor calcium release channel , Senile Dementia , Subiculum , Synaptic Transmission Title: Control of IsAHP in mouse hippocampus CA1 pyramidal neurons by RyR3 -mediated calcium -induced calcium release. PMID: 17562071 Related Articles Authors: Van de Vrede, Y , Fossier, P , Baux, G , Jols, M , Chameau, P Journal: Pflugers Arch , Vol. 455 (2): 297-308 , 2007 Abstract: In several neuronal preparations, the ryanodine-sensitive calcium store was reported to participate in the generation of slow afterhyperpolarization currents (IsAHP) involved in spike frequency adaptation. We show that calcium release from the ryanodine-sensitive calcium store is a major determinant of the triggering of IsAHP in mouse CA1 pyramidal neurons . Whole-cell patch clamp recordings in hippocampus slices show that the intracellular calcium stores depletion using an inhibitor of the endoplasmic reticulum Ca2+-ATPase (5 microM cyclopiazonic acid), as well as the specific blockade of ryanodine receptors (100 microM ryanodine ) both reduced the IsAHP by about 70%. Immunohistology, using an anti- RyR3 specific antibody, indicates that RyR3 expression is particularly enriched in the CA1 apical dendrites (considered as the most important site for sAHP generation). We show that our anti- RyR3 antibody acts as a functional RyR3 antagonist and induced a reduction in IsAHP by about 70%. The additional ryanodine application (100 micro M) did not further affect IsAHP, thus excluding RyR2 in IsAHP activation. Our results argue in favor of a specialized function of RyR3 in CA1 pyramidal cells in triggering IsAHP due to their localization in the apical dendrite. Affiliation: Laboratoire de Neurobiologie Cellulaire et Molculaire, CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette , France . Pubmed MeSH: Action Potentials , Amino Acid Sequence , Animals , Calcium Channels , Electrophysiology , Neuronal Plasticity , Patch-Clamp Techniques , Protein Isoforms , Synapses Wikipedia: Ammon's horn , Antibodies , Antibody , B cell receptor , Calcium , Calcium-induced calcium release , Calcium metabolism , Constriction , Cornu ammonis , Dendrite , Endoplasmic Reticulum , Ergastoplasm , Hippocampal formation , Hippocampus , House Mouse , House mice , Immunoglobulin , Intracellular , Laboratory mice , Laboratory mouse , Localization , Mice , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Nerve cell , Neuron , Opsonin , Protoplasm , Pyramidal cell , RyR1 , RyR2 , RyR3 , Ryanodine , Ryanodine receptor , Ryanodine receptor calcium release channel , Subiculum Title: Postsynaptic IP3 receptor -mediated Ca2+ release modulates synaptic transmission in hippocampal neurons . PMID: 15857686 Related Articles Authors: Kelly, P T , Mackinnon, R L , Dietz, R V , Maher, B J , Wang, J Journal: Brain Res Mol Brain Res , Vol. 135 (1-2): 232-48 , 2005 Abstract: Ca(2+)-dependent mechanisms are important in regulating synaptic transmission. The results herein indicate that whole-cell perfusion of inositol 1,4,5-trisphosphate receptor (IP(3)R) agonists greatly enhanced excitatory postsynaptic current (EPSC) amplitudes in postsynaptic hippocampal CA1 neurons . IP(3)R agonist-mediated increases in synaptic transmission changed during development and paralleled age-dependent increases in hippocampal type-1 IP(3)Rs. IP(3)R agonist-mediated increases in EPSC amplitudes were inhibited by postsynaptic perfusion of inhibitors of Ca(2+)/calmodulin, PKC and Ca(2+)/calmodulin-dependent protein kinase II. Postsynaptic perfusion of inhibitors of smooth endoplasmic reticulum (SER) Ca(2+)-ATPases, which deplete intracellular Ca(2+) stores, also enhanced EPSC amplitudes. Postsynaptic perfusion of the IP(3)R agonist adenophostin ( AdA ) during subthreshold stimulation appeared to convert silent to active synapses ; synaptic transmission at these active synapses was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Postsynaptic IP(3)R-mediated Ca(2+) release also produced a significant increase in spontaneous EPSC frequency. These results indicate that Ca(2+) release from intracellular stores play a key role in regulating the function of postsynaptic AMPARs. Affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence , KS 66045-2106, USA . ptkelly@ku.edu Pubmed MeSH: 2-Amino-5-phosphonovalerate , Adenosine , Age Factors , Animals , Animals, Newborn , Bicuculline , Blotting, Western , Calcium , Calcium Channel Agonists , Calcium Channels , Drug Interactions , Electric Stimulation , Enzyme Inhibitors , Excitatory Amino Acid Antagonists , Excitatory Postsynaptic Potentials , GABA Antagonists , Gene Expression Regulation, Developmental , Hippocampus , Indoles , Patch-Clamp Techniques , Picrotoxin , Rats , Receptors, Cytoplasmic and Nuclear , Thapsigargin , Time Factors Wikipedia: Agranular endoplasmic reticulum , CNQX , Calmodulin kinase , Endoplasmic Reticulum , Endoplasmic reticulum, smooth , Ergastoplasm , IP3 receptor , Inositol , Inositol 1,4,5-triphosphate , Inositol 1,4,5-trisphosphate , Inositol metabolism , Inositol triphosphate receptor , Kinase , Nerve cell , Neuron , Perfusion , Phosphotransferases , Protein Kinase , Protein kinases , Proteins , Smooth endoplasmic reticulum , Synapse , Synaptic Transmission Title: Capacitative calcium entry induces hippocampal long term potentiation in the absence of presenilin-1 . PMID: 12902342 Related Articles Authors: Ris, L , Dewachter, I , Reverse, D , Godaux, E , Van Leuven, F Journal: J Biol Chem , Vol. 278 (45): 44393-9 , 2003 Abstract: Presenilins, whose mutant forms are the most common cause of early onset familial Alzheimer's disease, are involved in two very distinct processes: (i) proteolytic activity as gamma-secretase acting on amyloid precursor protein to produce amyloid peptides and (ii) storage of Ca2+ in the endoplasmic reticulum (ER). In particular, absence of presenilin-1 ( PS1 ) was claimed to potentiate capacitative calcium entry (CCE), i.e. the mechanism of replenishment of ER Ca2+ stores. However, until now, evidence in favor of the latter role has been obtained only in isolated or cultured cells and not on neurons in situ. Here, we studied the strength of the synapses between Schaffer's collaterals and CA1 neurons in hippocampal slices when they were submitted first to Ca(2+)-free medium containing thapsigargin and subsequently to normal artificial cerebrospinal fluid, a procedure known to trigger CCE. We demonstrate that Ca2+ influx via the CCE mechanism is sufficient to trigger robust long term potentiation of the synapses in hippocampal slices from transgenic mice with a postnatal, neuron-specific ablation of PS1 , but remarkably not from wild-type mice. Our data establish for the first time in neurons confined in normal neuronal networks that PS1 acts on the refilling mechanism of ER Ca2+ stores. Affiliation: Laboratory of Neuroscience, University of Mons - Hainaut , B-7000 Mons, Belgium . Pubmed MeSH: Animals , Hippocampus , Long-Term Potentiation , Membrane Proteins Wikipedia: Alpha-secretase , Alpha secretase , Alzheimer's Disease , Alzheimer disease , Amyloid , Beta-secretase , Beta secretase , Calcium , Calcium metabolism , Cells, cultured , Cerebrospinal Fluid , Endoplasmic Reticulum , Ergastoplasm , Gamma-Secretase , Gamma secretase , House Mouse , House mice , Laboratory mice , Laboratory mouse , Methods , Mice , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Nerve cell , Neuron , Peptides , Polypeptides , Presenile dementia , Presenilin , Procedure , Proteins , Secretase , Senile Dementia , Synapse , Thapsigargin , Transgene Title: PMID: 12723356 Related Articles Authors: Popov, V I , Medvedev, N I , Rogachevskii, V V , Ignat'ev, D A , Stewart, M G , Fesenko, E E Journal: Biofizika , Vol. 48 (2): 289-308 , 2003 Mar-Apr Abstract: The literature data and our own data on the synaptic plasticity and remodeling of synaptic organelles in the central nervous system are reviewed. Modern techniques of laser scanning confocal microscopy and serial thin sectioning for in vivo and in vitro studies of dendritic spines, including the relationship between morphological changes and the efficacy of synaptic transmission, are discussed using, in particular, a model of long-term potentiation. The organization of dendritic spines and postsynaptic densities of different categories as well as the role of filopodia in spine genesis were analyzed. It was shown that the method of serial ultrathin sections is the most effective for unbiased quantitative stereological analysis and 3D reconstructions. By using the refined method of serial ultrathin sections with subsequent three-dimensional reconstructions, the presence of giant mitochondria in hippocampal neuronal dendrites was demonstrated. It was shown that smooth endoplasmic reticulum forms a unified continuum with the outer membrane of the mitochondrial envelope within dendrites. It was suggested that this continuum provides calcium tunneling, which makes possible intracellular signal transduction during synaptic transmission. Evidence is presented indicating the presence of gap junctions ( electrical synapses ) in the synapses of mammalian brain, as well as between glial processes, and between glial cells and neurons . Our data and the data of other authors show that glial cell processes form a structural and functional glial network, which modulates the functioning of the neuronal network. The connection of dendritic spines with the glial network is shown on 3D reconstructions by analyzing the neuropil volume in CA1 hippocampal area of ground squirrels in three functional states: normothermia, provoked arousal, and hibernation when brain temperature falls below 6 degrees C. The own data of the authors are discussed indicating the formation of more than five presynaptic boutons (multiple synapses ) on both CA1 mushroom-like dendritic spines and CA3 thorny excrescences. On the basis of the analysis, new ideas of the organization and functioning of synapses were suggested. Affiliation: Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia . popvi@mail.ru Pubmed MeSH: Animals , Gerbillinae , Hibernation , Rats , Species Specificity Wikipedia: Agranular endoplasmic reticulum , Ammon's horn , Anxiety , Astrocyte , Astroglia , Calcium , Calcium metabolism , Confocal Microscopy , Confocal laser scanning microscopy , Cornu ammonis , Dendrite , Dendritic spine , Electrical synapse , Endoplasmic Reticulum , Endoplasmic reticulum, smooth , Ergastoplasm , Filopodia , Gap junction , Glia , Glial Cells , Glial cell , Hippocampal formation , Hippocampus , Lamellipodia , Laser , Lobopodia , Long-term potentiation , Long term potentiation , Maser , Membrane , Microscopy , Microscopy, confocal , Microtomy , Mitochondria , Mitochondrion , Nerve cell , Nervousness , Neuroglia , Neuron , Neuropil , Organelle , Plastic , Pseudopodia , Pseudopodium , Pulsed laser , Q-switched laser , Smooth endoplasmic reticulum , Subiculum , Synapse , Synaptic Transmission , Temperature , Ultramicrotomy , Underweight Title: Calcium /calmodulin-dependent protein kinase II clusters in adult rat hippocampal slices. PMID: 12421609 Related Articles Authors: Tao-Cheng, J H , Vinad, L , Pozzo Miller, L D , Reese, T S , Dosemeci, A Journal: Neuroscience , Vol. 115 (2): 435-40 , 2002 Abstract: We have previously reported the formation of calcium /calmodulin-dependent protein kinase II ( CaMKII ) clusters approximately 110 nm in diameter in hippocampal neurons in culture and in the intact adult brain, under conditions that simulate ischemic stress and increase (i) . These observations suggest that ischemia-like conditions that prevail during the dissection of brain tissue for the preparation of hippocampal slices could lead to the formation of CaMKII clusters. We now show by pre-embedding immuno-electron microscopy that, indeed, CaMKII clusters are present in the CA1 pyramidal neurons in hippocampal slices from adult rats fixed immediately after dissection, and that the number of CaMKII clusters increases with the delay time between decapitation and fixation. Moreover, CaMKII clusters are typically localized near the endoplasmic reticulum . When acute slices are allowed to recover in oxygenated medium for 2 h, CaMKII clusters mostly disappear, indicating that clustering is reversible. Also, the postsynaptic density, another site for CaMKII accumulation under excitatory conditions, becomes thinner upon recovery. Treatment of recovered slices with high potassium for 90 s causes the re-appearance of CaMKII clusters in nearly all CA1 pyramidal cells examined. On the other hand, when dissociated hippocampal neurons in primary culture are exposed to the same depolarizing conditions, only approximately 25% of neurons exhibit CaMKII clusters, indicating a difference in the susceptibility of the neurons in culture and in acute slices to excitatory stimuli. Altogether these observations indicate that the effect of CaMKII clustering should be considered when interpreting experimental results obtained with hippocampal slices. Affiliation: Laboratory of Neurobiology, NINDS, NIH, Building 36, Room 2A21, Bethesda , MD 20892, USA . chengs@ninds.nih.gov Pubmed MeSH: Age Factors , Animals , Cells, Cultured , Culture Media , Hippocampus , Microscopy, Electron , Organ Culture Techniques , Rats , Rats, Sprague-Dawley , Synapses Wikipedia: Adult , CaMKII , CaM KII , CaM Kinase II , Calmodulin kinase , Cluster Analysis , Cluster analyses , Clustering , Decapitation , Dioxygen , Dissection , Dissociation , Dissociative Disorders , Dissociative disorder , Endoplasmic Reticulum , Ergastoplasm , Fugue , Kinase , Microscopy , Nerve cell , Neuron , Neuroscience , Oxygen , Oxygen metabolism , Oxygenator , Phosphotransferases , Potassium , Potassium Metabolism , Protein Kinase , Protein kinases , Proteins , Pyramidal cell , Tissue Title: Release and sequestration of calcium by ryanodine-sensitive stores in rat hippocampal neurones. PMID: 9234194 Related Articles Authors: Garaschuk, O V , Yaari, Y , Konnerth, A Journal: J Physiol , Vol. 502 ( Pt 1) , 1997 Abstract: 1. The properties of ryanodine-sensitive Ca2+ stores in CA1 pyramidal cells were investigated in rat hippocampal slices by using whole-cell patch-clamp recordings combined with fura-2-based fluorometric digital imaging of cytoplasmic Ca2+ concentration ( i). 2. Brief pressure applications of caffeine onto the somata of pyramidal cells caused large transient increases in i (Ca2+ transients) of 50-600 nM above baseline. 3. The Ca2+ transients evoked by caffeine at -60 mV were not associated with an inward current, persisted after blocking voltage-activated Ca2+ currents and were completely blocked by bath-applied ryanodine. Similar transients were also evoked at +60 mV. Thus, these transients reflect Ca2+ release from intracellular ryanodine-sensitive Ca2+ stores. 4. The Ca2+ transients evoked by closely spaced caffeine pulses rapidly decreased in amplitude, indicating progressive depletion of the Ca2+ stores. The amplitude of the Ca2+ transients recovered spontaneously with an exponential time constant of 59 s. Recovery was accelerated by depolarization-induced elevations in i and blocked by cyclopiazonic acid (CPA) and thapsigargin, indicating that store refilling is mediated by endoplasmic reticulum Ca(2+)-ATPases. 5. Even without prior store depletion the caffeine-induced Ca2+ transients disappeared after 6 min exposure to CPA, suggesting that ryanodine-sensitive Ca2+ stores are maintained at rest by continuous Ca2+ sequestration. 6. Caffeine-depleted Ca2+ stores did not refill in Ca(2+)-free saline, suggesting that the refilling of the stores depends upon Ca2+ influx through a 'capacitative-like' transmembrane influx pathway operating at resting membrane potential. The refilling of the stores was also blocked by Ni2 + and gallopamil (D600). 7. Elevations of basal i produced by bath-applied KCl markedly potentiated (up to 6-fold) the caffeine-induced Ca2+ transients. The degree of potentiation was positively related to the increase in basal i. The Ca2+ transients remained potentiated up to 9 min after reversing the KCl-induced i increase. Thus, the ryanodine-sensitive Ca2+ stores can 'overcharge' when challenged with an increase in i and slowly discharge excess Ca2+ after basal i returns to its resting level. 8. Pressure applications of caffeine onto pyramidal cell dendrites evoked local Ca2+ transients similar to those separately evoked in the respective somata. Thus, dendritic ryanodine-sensitive Ca2+ stores are also loaded at rest and can function as independent compartments. 9. In conclusion, the ryanodine-sensitive Ca2+ stores in hippocampal pyramidal neurones contain a releasable pool of Ca2+ that is maintained by a Ca2+ entry pathway active at subthreshold membrane potentials. Ca2+ entry through voltage-gated Ca2+ channels transiently overcharges the stores. Thus, by acting as powerful buffers at rest and as regulated sources during activity, Ca2+ stores may control the waveform of physiological Ca2+ signals in CA1 hippocampal pyramidal neurones. Affiliation: I Physiologisches Institut, Universitt des Saarlandes, Homburg , Germany . Pubmed MeSH: Animals , Calcium Channels , Calmodulin-Binding Proteins , Central Nervous System Stimulants , Enzyme Inhibitors , Hippocampus , Indoles , Muscle Proteins , Potassium , Rats , Rats, Wistar , Ryanodine Receptor Calcium Release Channel , Synapses Wikipedia: 1,3,7-trimethylxanthine , Acceleration , Caffeine , Calcium , Calcium metabolism , Cytoplasm , D600 , Dendrite , Endoplasmic Reticulum , Ergastoplasm , Membrane , Membrane potential , Nerve cell , Neuron , Patch-clamp technique , Pressure , Protoplasm , Pulse , Pyramidal cell , Resting membrane potential , Resting potential , Ryanodine , Salinity , Thapsigargin , Transmembrane potential , Transmembrane potential difference , Vivarin Title: Three-dimensional organization of smooth endoplasmic reticulum in hippocampal CA1 dendrites and dendritic spines of the immature and mature rat. PMID: 8987748 Related Articles Authors: Spacek, J , Harris, K M Journal: J Neurosci , Vol. 17 (1): 190-203 , 1997 Abstract: Recent studies have shown high levels of calcium in activated dendritic spines, where the smooth endoplasmic reticulum (SER) is likely to be important for regulating calcium . Here, the dimensions and organization of the SER in hippocampal spines and dendrites were measured through serial electron microscopy and three-dimensional analysis. SER of some form was found in 58% of the immature spines and in 48% of the adult spines. Less than 50% of the small spines at either age contained SER, suggesting that other mechanisms, such as cytoplasmic buffers, regulate ion fluxes within their small volumes. In contrast, 80% of the large mushroom spines of the adult had a spine apparatus, an organelle containing stacks of SER and dense-staining plates. Reconstructed SER occupied 0.001-0.022 microm3, which was only 2-3.5% of the total spine volume; however, the convoluted SER membranes had surface areas of 0.12-2.19 microm2, which were 12 to 40% of the spine surface area. Coated vesicles and multivesicular bodies occurred in some spines, suggesting local endocytotic activity. Smooth vesicles and tubules of SER were found in continuity with the spine plasma membrane and margins of the postsynaptic density (PSD), respectively, suggesting a role for the SER in the addition and recycling of spine membranes and synapses . The amount of SER in the parent dendrites was proportional to the number of spines and synapses originating along their lengths. These measurements support the hypothesis that the SER regulates the ionic and structural milieu of some, but not all, hippocampal dendritic spines. Affiliation: Department of Pathology, Charles University Medical Faculty Hospital, CZ-500 05 Hradec Kralove , Czech Republic . Pubmed MeSH: Aging , Animals , Endocytosis , Exocytosis , Hippocampus , Humans , Rats , Rats, Inbred Strains Wikipedia: Adult , Agranular endoplasmic reticulum , Calcium , Calcium metabolism , Cell Membrane , Cell membranes , Cytoplasm , Cytoplasmic membrane , Dendrite , Dendritic spine , Electron , Electron Microscopy , Electronic , Endoplasmic Reticulum , Endoplasmic reticulum, smooth , Ergastoplasm , Ions , Membrane , Microscopy , Microscopy, electron , Negatron , Parent , Plasma membrane , Positron , Protoplasm , Smooth endoplasmic reticulum , Step-parent , Stepparent , Synapse Page 1 2 Title: Cytosolic Ca2+ binding proteins during rat brain ageing: loss of calbindin and calretinin in the hippocampus, with no change in the cerebellum. PMID: 8000572 Related Articles Authors: Villa, A , Podini, P , Panzeri, M C , Racchetti, G , Meldolesi, J Journal: Eur J Neurosci , Vol. 6 (9): 1491-9 , 1994 Abstract: The expression of two cytosolic, high affinity Ca(2+)-binding proteins, calbindin-28 and calretinin, has been investigated in the cerebellum and hippocampus of young and old rats (from 12 days to 30 months) by combining immunofluorescence and Western blotting. Three markers, calreticulin (the major Ca2+ binding protein within the lumen of the endoplasmic reticulum ), MAP-2 (a microtubule binding protein concentrated in neuronal dendrites ) and synaptophysin (an integral protein of synaptic vesicles), were studied in parallel. In the cerebellar cortex a rise from 12 to 60 days was observed with calbindin-28 and, especially, calretinin, concentrated in the Purkinje and granule neurons , respectively. The level of expression of the two proteins subsequently remained high and the distribution was unchanged, even in the cerebellum of old animals. A completely different pattern was observed in the hippocampus. Here calretinin, present especially in fibres and interneurons, was abundant in the young, decreased in the adult and reached low values in the old rats. Calbindin-28 accumulated during growth, especially in a subpopulation of CA1 pyramidal cells and in the mossy fibres of CA3, then declined, although irregularly, during ageing. These changes of the two proteins were more marked in the dorsal and central parts than in the ventral part of the hippocampus. In the same brain areas the levels of expression of the three additional markers and their distribution within neurons and synapses were unchanged by ageing.(ABSTRACT TRUNCATED AT 250 WORDS) Affiliation: Department of Pharmacology, CNR Cytopharmacology, Milan , Italy . Pubmed MeSH: Aging , Brain , Calcium-Binding Protein, Vitamin D-Dependent , Calcium-Binding Proteins , Immunohistochemistry , Rats , Rats, Sprague-Dawley Wikipedia: Adult , Ammon's horn , Animal , Animalia , Binding protein , Blotting, western , Calreticulin , Carrier proteins , Cellular senescence , Cerebellar cortex , Cerebellum , Cornu ammonis , Cytosol , Dendrite , Endoplasmic Reticulum , Ergastoplasm , Fluorescent antibody technique , Hippocampal formation , Hippocampus , Immunofluorescence , Interneuron , Microtubule , Nerve cell , Neuron , Proteins , Pyramidal cell , Subiculum , Synapse , Synaptic vesicle , Synaptophysin , Western Blot , Western blotting Page 1 2 对100篇相关文献的计量分析结果: Top Countries Publications USA 53 United Kingdom 8 Japan 7 Germany 7 Canada 7 France 4 Sweden 3 Italy 2 New Zealand 2 Spain 2 Netherlands 1 Switzerland 1 Taiwan 1 China 1 Argentina 1 1 2 3 4 Top Cities Publications New York 6 Boston 6 Bethesda 5 Montreal 4 Valhalla 3 London 3 Birmingham, USA 3 Aurora 2 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Receptors, Glutamate 48 Pyramidal Cells 47 N-methyl-D-aspartate selective glutamate receptor activity 47 Depression 46 Receptors, N-Methyl-D-Aspartate 46 Neuronal Plasticity 46 Dendritic Spines 45 Long-Term Potentiation 44 1 2 3 ... 52 Top Terms Publications long-term synaptic potentiation 42 dendritic spine membrane 42 dendritic spine 41 Excitatory Postsynaptic Potentials 40 Patch-Clamp Techniques 35 Receptors, Metabotropic Glutamate 35 Electric Stimulation 34 pyramidal neuron development 31 pyramidal neuron differentiation 30 pyramidal neuron migration 30 receptor activity 30 synaptic transmission 30 Rats, Sprague-Dawley 30 signal transduction 29 long term synaptic depression 28 Receptors, AMPA 27 alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex 27 alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid 27 Proteins 26 Excitatory Amino Acid Antagonists 26 1 2 3 4 ... 52 Top Terms Publications Action Potentials 25 hippocampus development 25 Calcium Signaling 24 nmda receptor 24 intracellular 23 ampa 22 Long-Term Synaptic Depression 22 learning 19 Mice 19 Membranes 17 membrane 17 Signal Transduction 17 Phosphotransferases 16 synapse 16 Cells, Cultured 16 positive regulation of synaptic plasticity 15 Rats, Wistar 15 Protein Kinases 14 Calcium Channels 14 learning or memory 13 1 2 3 4 5 ... 52 Top Years Publications 2006 13 2007 12 2005 11 2009 10 2008 9 2004 6 2001 6 2002 6 2000 6 1999 5 2003 3 1992 3 1996 3 1998 3 1988 1 1997 1 1993 1 1995 1 Top Terms Publications postsynaptic density 13 glutamate receptor activity 13 Organ Culture Techniques 13 mglur 13 regulation of excitatory postsynaptic membrane potential 12 Interneurons 12 regulation of action potential in neuron 12 regulation of action potential 12 positive regulation of action potential 12 negative regulation of action potential 12 Microscopy 12 Inositol 1,4,5-Trisphosphate Receptors 11 PLC activating metabotropic glutamate receptor activity 11 Membrane Potentials 11 Inositol 10 Calcium Channels, L-Type 10 Glutamic Acid 10 Time Factors 10 metabotropic glutamate receptor 10 regulation of synaptic plasticity 9 1 2 3 4 5 6 ... 52 Top Terms Publications Glycine 9 Fluorescence 9 positive regulation of dendrite morphogenesis 9 Neural Inhibition 9 Probability 9 Inositol 1,4,5-Trisphosphate 8 nmdar 8 Humans 8 ionotropic glutamate receptor activity 8 Electrophysiology 8 Actins 7 protein serine/threonine kinase activity 7 pka 7 actin 7 Mice, Knockout 7 nr2b 7 Ryanodine 7 Endoplasmic Reticulum 7 Green Fluorescent Proteins 7 endoplasmic reticulum 7 1 2 3 4 5 6 7 ... 52 Top Terms Publications extracellular region 7 Transfection 7 Receptors, Neurotransmitter 7 Adult 7 Calcium-Calmodulin-Dependent Protein Kinase Type 2 7 6-Cyano-7-nitroquinoxaline-2,3-dione 7 positive regulation of synaptic transmission 7 Presynaptic Terminals 7 glutamate receptor 7 Electrons 7 Electronics 7 Axons 7 axon 7 Mossy Fibers, Hippocampal 6 Cyclic AMP-Dependent Protein Kinases 6 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